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Frisch, Kristina. "Klonierung von IL-10 und IL-10-Homologen und Funktionsanalyse in einem Mausmodell der polymikrobiellen Sepsis." [S.l.] : [s.n.], 2004. http://deposit.ddb.de/cgi-bin/dokserv?idn=973392185.
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Ng, Tien Haeng Sky. "Mechanisms of IL-10 transcriptional regulation." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.702135.
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Previous work has shown that subcutaneous (s.c) specific immunotherapy (SIT) using the myelin protein peptide MBP Acl-9 [4Y] induces protection against EAE in the TCR transgenic Tg4 mice. Repeated administration of MBP Ac1-9 [4Y] was found to induce IL-1O expressing TH1 like cells which were termed IL-l0 Tregs. To further the understanding of how IL-1O transcription is regulated, the expression of IFN-y, IL-4, IL-1O, c-Maf, NFIL3 protein and mRNA, Gata3 mRNA and epigenetic modifications at the Il10 promoter were characterised for each dose of s.c MBP Ac 1-9 [4 Y] administration. The analysis revealed that c-Maf and NFIL3 positively correlated with Il-IO expression, whilst levels of H3K27me3 at the Il10 promoter, an epigenetic mark associated with transcriptional repression, correlated inversely with IL-IO expression. To investigate the therapeutic potential of non-antigen specific immunoregulatory small molecules, GSK3 inhibitors were co-cultured with murine TH1, TH2 and human memory T cells. The analysis shows that GSK3 inhibitors also induce IL-10 expression via transcriptional mechanisms in both murine Th cells and human memory T cells. Similar to IL-l0 Tregs, murine TH1 GSK3 inhibitor treated cells expressed higher levels of NFIL3 and c-Maf whilst murine TH2 GSK3 inhibitor treated cells expressed higher levels of NFIL3 only. In contrast to IL-10 Tregs both THI and TH2 cells expressed higher levels of Gata3 in response to GSK3 inhibitor treatment. In addition, epigenetic changes also take place in the Il10 promoter of GSK3 inhibitor treated murine TH1 and human memory T cells. Collectively these results show that it is possible to alter epigenetic modifications and induce IL-1O expression in murine TH1 and TH1-like cells with in vivo and in vitro methods. Furthermore, we propose combining the antigen specific s.c SIT with GSK3 inhibitors to improve the efficacy and safety of both treatments.
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Cordeiro, Cynthia Azeredo. "Polimorfismos dos Genes das Citocinas IL-1alfa, IL -1beta, IL-10 e TNF-alfa." Universidade Federal de Minas Gerais, 2008. http://hdl.handle.net/1843/RRSA-7F5KG7.
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Purpose: Toxoplasmic Retinochoroiditis (TR) is the most common identifiable cause of posterior uveitis in many parts of the world. There is a great controversy regarding which factors are responsible for the occurrence or reccurrence of TR. Experimental data have demonstrated a relevant role for IL-10, TNF-alfa, IL-1alfa and IL-1alfa in the modulation of acute ocular toxoplasmosis. Therefore, we aim to investigate thepossible association between an IL10 (-1082G/A), TNF-alfa (-308G/A), IL1A (-889C/T) and IL1B (+3954C/T) gene polymorphisms and TR in humans. Methods: One hundred patients with diagnosed TR were recruited from the Uveitis Section, Federal University of Minas Gerais. For comparison, one hundred healthy blood donors with positive serology for Toxoplasmosis and without retinal signs of previous TR were included in the study. Genomic DNA was obtained from oral swabs of individualsand amplified using polymerase chain reaction (PCR) with specific primers for each locus gene. PCR products were submitted to restriction endonuclease digestion and analyzed by polyacrylamide gel electrophoresis to distinguish specific alleles for eachgene, allowing the detection of the polymorphism and determination of genotypes.Results: In the IL10 gene polymorphism analysis, there was a significant difference in the genotype distribution between TR patients and control subjects (x² = 6.33, P = 0.04). Carriers of the IL10 -1082 A allele (AA + AG genotypes) were more often patients with TR than controls (x² = 5.97, P = 0.01, OR = 2.55, CI = 1.11
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Wong, Li-Chuen. "IL-10 promoter polymorphisms in atopic dermatitis." Thesis, The University of Sydney, 2002. https://hdl.handle.net/2123/27849.
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Atopic dermatitis (AD) is one of the many clinical manifestations of atopy. It is one of the most common chronic inflammatory skin diseases with increasing prevalence over the last century. The aetiology of this disease is multifactorial with a complex interaction of genetic, environmental and immunologic factors.
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Saramago, Eduardo Alves. "O hidrogênio molecular potencializa a hipotermia e previne a hipotensão e a febre durante a inflamação sistêmica induzida por LPS." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/17/17134/tde-07022019-140036/.
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O hidrogênio molecular (H2) exerce efeito antioxidante, anti-apoptótico e antiinflamatório. Nesse estudo testamos a hipótese que o H2 modula as mudanças cardiovasculares, inflamatórias e termorregulatórias na inflamação sistêmica (IS) induzida por lipopolissacarídeo (LPS) em diferentes doses (0,1 ou 1,5 mg/kg, intravenoso, induzindo IS moderada ou severa) em ratos machos Wistar (250-300 g). LPS ou salina foi injetada imediatamente antes do início dos 360 minutos de inalação do H2 (2% H2, 21% O2, balanceado com nitrogênio) ou ar ambiente (21% O2, balanceado com nitrogênio). A temperatura corporal (Tc) foi mensurada por datalogger pré-implantados na cavidade peritoneal. O H2 não causou mudança nos parâmetros cardiovasculares, inflamatórios e na Tc dos ratos controle (tratados com salina). Durante a IS moderada o H2 reduziu o surgimento das citocinas pró-inflamatórias no plasma (TNF-? e IL-6) enquanto causou um aumento da IL-10 plasmática (citocina anti-inflamatória) e preveniu a febre. Durante a IS severa o H2 potencializou a hipotermia e preveniu a febre e a hipotensão. Além disso, o H2 causou uma redução no surgimento das citocinas pró-inflamatórias (TNF-? e IL-1? do plasma) e prostaglandina E2 [(PGE2), no plasma e no hipotálamo], e um aumento da IL-10 plasmática. Esses dados são consistentes com o entendimento que o H2 atenua a febre na IS moderada e durante a IS severa potencializa a hipotermia, previne a hipotensão e exerce um efeito antiinflamatório forte o suficiente para prevenir a febre alterando a sinalização febrigênica e alterando a produção hipotalâmica de PGE2Molecular hydrogen (H2) exerts anti-oxidative, anti-apoptotic, and anti-inflammatory effects. Here we tested the hypothesis that H2 modulates cardiovascular, inflammatory, and thermoregulatory changes in systemic inflammation (SI) induced by lipopolysaccharide (LPS) at different doses (0.1 or 1.5 mg/kg, intravenously, to induce mild or severe SI) in male Wistar rats (250-300 g). LPS or saline was injected immediately before the beginning of 360- minute inhalation of H2 (2% H2, 21% O2, balanced with nitrogen) or room air (21% O2, balanced with nitrogen). Deep body temperature (Tb) was measured by dataloggers preimplanted in the peritoneal cavity. H2 caused no change in cardiovascular, inflammatory parameters, and Tb of control rats (treated with saline). During mild SI, H2 reduced plasma surges of proinflammatory cytokines (TNF-? and IL-6) while caused an increase in plasma IL-10 (anti-inflammatory cytokine) and prevented fever. During severe SI, H2 potentiated hypothermia, and prevented fever and hypotension. Moreover, H2 caused a reduction in surges of proinflammatory cytokines (plasma TNF-? and IL-1?) and prostaglandin E2 [(PGE2), in plasma and hypothalamus], and an increase in plasma IL-10. These data are consistent with the notion that H2 blunts fever in mild SI, and during severe SI potentiates hypothermia, prevents hypotension and exerts anti-inflammatory effects strong enough to prevent fever by altering febrigenic signaling and ultimately down-modulating hypothalamic PGE2 production
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Vale, Mariana Lima. "Atividade analgesica das interleucinas 4, 10 e 13 (IL-4, IL-10 e il-13) na dor inflamatoria experimental : papel de celulas residentes e citocinas." reponame:Repositório Institucional da UFC, 2000. http://www.repositorio.ufc.br/handle/riufc/2569.
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VALE, Mariana Lima. Atividade analgesica das interleucinas 4, 10 e 13 (IL-4, IL-10 e il-13) na dor inflamatoria experimental : papel de celulas residentes e citocinas. 2000. 140 f. Dissertação (Mestrado em Farmacologia) - Universidade Federal do Ceará. Faculdade de Medicina, 2000.Submitted by denise santos (denise.santos@ufc.br) on 2012-05-04T12:19:28Z No. of bitstreams: 1 2000_dis_mlvale.pdf: 664941 bytes, checksum: a8df00b6a53f2d6632ebe816657800aa (MD5)
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The release of cyclo-oxigenase products and sympathomimetics amines, the final mediators of inflammatory pain, is preceded by the generation of cytokines by resident cells. In recent years a number of cytokines such as IL-4, IL-10, IL-13, IL-6, TGF-β e IFN-α have been described to inhibit the production of TNF-α, IL-1β, IL-6 and IL-8 (cytokines regarded as pró-inflammatory) and possibly to exert their modulatory effect on macrophages and mast cells. Since it is known the capacity of those cytokines to inhibit the production of pro-inflammatory cytokines and the pivotal role of resident cells in the development of inflammatory pain we have decided to test the possibility of IL-4, IL-13 and IL-10 to modulate inflammatory pain. In short, IL-4 (1 – 5ng/animal), IL-13 (0.4 - 2.5ng/animal) or IL-10 (0.4 - 10ng/animal) was given 30 min before acetic acid (AAc) or zymosan (Zym) administration in the writhing model. IL-4 (2.5 e 5 ng/animal), IL-13 (1 e 2.5 ng/animal) or IL-10 (2 e 10 ng/animal) were injected, ip, 30 min before Zym (1 mg/animal; intra-articular) in the rat knee joint incapacitation test up to the 4th hour (the number of leukocytes was determined in the articular exsudate 6 hours later). Doses of those cytokines that exerted maximum effect in the writhing test were also injected 30 min before the hot plate test. These same doses were injected ip before naloxone administration in the AAc-induced writhing model in mice. TNF-α and IL-1β were determined in the supernatant of a macrophage culture which were collected from peritoneal fluid of mice treated with Zym and pre-treated with the cytokines under test. Our results show that interleukins 4, 13 and 10 inhibit writhing response in mice induced by AAc or Zym up to 58.7, 89.2 and 52%, and up to 62.6, 61.7 and 74.4%, respectively (p<0.05). Similar results were observed in the rat knee joint incapacitation test induced by Zym: 49.2, 56.6, 69,9% of inhibition (p<0.05). The same interleukins were able to inhibit Zym-induced leukocyte influx into articular cavity (53.8, 92.1 e 62% of inhibition, respectively - p<0,05). The analgesic activity of IL-4, IL-13 and IL-10 seems to be peripheral, since these cytokines presented no effect in the reaction time of the animals on hot plate test. This antinociceptive effect seems to have no relation with endogen opioid release since naloxone (opioid receptor antagonist) had no effect in reverting the antinociceptive effect of cytokines in the AAc-induced writhing in mice. However, IL-4 and IL-10 inhibit the release of TNF-α (42 e 41.2%, respectively - p<0.05) and of IL-1β (61.9 e 80.9%, respectively - p<0,05) by macrophages stimulated in vivo by Zym, indicating that their antinociceptive activities may be due to the inhibition of those cytokines release by resident cells.
Já está estabelecido que a liberação de produtos da cicloxigenase e aminas simpatomiméticas, mediadores finais da dor inflamatória é precedido pela geração, por células residentes, de uma cascata de citocinas. Recentemente dados do nosso laboratório demonstraram que no modelo de contorções abdominais (CA) a ativação dessa cascata é dependente também da presença de células residentes como macrófagos e mastócitos. Dados da literatura apontam algumas citocinas capazes de modular negativamente a função dessas células: IL-4,. IL-10, IL-13, IL-6, TGF-β e IFN-α . Com base nesses dados, o objetivo do presente trabalho foi estudar uma possível atividade analgésica de três citocinas: IL-4, IL-13 e IL-10. Para tanto injetou-se, via ip, IL-4 (1–5ng/animal), IL-13 (0.4-2.5ng/animal) ou IL-10 (0.4-10ng/animal) 30 min antes da administração de zymosan (Zym) ou ácido acético (AAc) para o teste de CA. IL-4 (2.5 e 5ng/animal), IL-13 (1 e 2.5ng/animal) ou IL-10 (2 e 10ng/animal) foi injetada, ip, 30 min antes do Zym (1 mg/animal; intra-articular) e logo após foi medida a incapacitação articular (IA) até a 4ª hora e na 6ª hora foi feita a contagem de leucócitos no fluido articular. As interleucinas estudadas também foram administradas (30 min antes) na dose que melhor inibiu as CA no teste da placa quente (PQ) e em camundongos que haviam recebido ou não a naloxona previamente ao estímulo (AAc) no teste de CA. IL-4 (5 ng/animal) ou IL-10 (10 ng/animal) foi injetada ip 30 min antes do Zym (ip) e após 15 min os animais foram sacrificados e o exsudato peritoneal foi colhido e posto em cultura para a dosagem de IL-1β e TNF-α no sobrenadante. No presente trabalho ficou demonstrado que as interleucinas-4, 13 e 10 são analgésicas tanto no modelo de CA induzidas por AAc (58.7, 89.2, 52% de inibição, efeito máximo, respectivamente, p<0.05) ou Zym (62.6, 61.7, 74.4% de inibição, efeito máximo, respectivamente, p<0.05) como também no modelo de IA induzido por Zym (49.2, 56.6, 69,9% de inibição, efeito máximo, respectivamente, p<0.05). As citocinas estudadas foram capazes de inibir o influxo de leucócitos para a cavidade articular (53.8, 92.1 e 62%, respectivamente - p<0,05). Foi demonstrado que o efeito analgésico parece ser de domínio periférico visto que nenhuma das citocinas modificou o tempo de reação na PQ, teste algesimétrico sensível apenas para drogas que exercem efeito central. Também foi demonstrado que a atividade analgésica das interleucinas testadas não depende da liberação de opióides endógenos, visto que o pré-tratamento com naloxona não foi capaz de reverter a atividade analgésica de nenhuma das interleucinas no modelo de CA. Contudo essa atividade analgésica parece depender da inibição da liberação de citocinas por células residentes visto que IL-4 e IL-10 foram capazes de diminuir a liberação de TNF-α (42 e 41.2% de inibição respectivamente - p<0.05) e IL-1β (61.9 e 80.9% de inibição respectivamente - p<0,05) por macrófagos peritoneais residentes.
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Costa, Tânia Alves da. "A função da IL-10 na paracoccidioidomise pulmonar murina." Universidade de São Paulo, 2010. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-16122010-113911/.
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O principal mecanismo de defesa de hospedeiros infectados pelo Paracoccidioides brasiliensis (Pb), fungo dimórfico que causa a mais importante micose sistêmica da América Latina, é a imunidade celular. Neste processo participam macrófagos ativados por IFN-g e a IL-10 parece ser a citocina que se contrapõe a esta ativação. Tanto na patologia humana como em modelos experimentais há fortes indicações de que a IL-10 age como supressora da imunidade celular causando efeitos deletérios aos hospedeiros; entretanto, estudos diretos sobre a função da IL-10 na paracoccidiodomicose (PCM) não tinham sido ainda realizados. Então o objetivo fundamental deste trabalho foi estudar a função da IL-10 nos mecanismos da imunidade inata e adaptativa contra o Pb utilizando como modelo experimental camundongos geneticamente deficientes de IL-10 (IL-10 nocaute, IL-10 KO) em comparação com seus controles normais (WT). Demonstramos in vitro que macrófagos peritoneais normais de camundongos IL-10 KO apresentam uma maior atividade fagocítica e fungicida que os macrófagos de camundongos WT e isto esteve associado à maior produção de IFN-g, TNF-α, óxido nítrico (NO) e da quimiocina MCP-1. Verificamos, entretanto, que a produção de IFN-g era realizada por células NKT contaminantes de macrófagos aderentes nos camundongos IL-10 KO, sugerindo uma possível participação destas células na ativação de macrófagos e de células T de camundongos IL-10 KO. Estudos in vivo revelaram que a partir da 2ª semana de infecção os camundongos IL-10 KO apresentaram uma resposta imune precoce em relação aos WT, pois os pulmões dos primeiros apresentavam carga fúngica significativamente menor, associada com aumento da maioria dos isótipos de anticorpos (IgM, IgG1, IgG2a, IgG2b) específicos contra o fungo. Observamos também a inibição total da produção das citocinas IL-4 e IL-5, mostrando a ação reguladora da IL-10 na síntese de citocinas Th2. Na 4ª semana pós-infecção a carga fúngica continuou menor nos animais IL-10 KO, mas não foram observadas as diferenças quanto à síntese de anticorpos entre as duas linhagens. A análise dos leucócitos infiltrantes nos pulmões revelou um aumento na frequência de linfócitos T CD4+ ativados nos camundongos IL-10 KO em relação aos WT. A partir da 8ª semana, a carga fúngica pulmonar dos camundongos IL-10 KO reduziu consideravelmente e não ocorreu disseminação para outros órgãos. Observou-se também, nesta linhagem, um aumento na resposta de hipersensibilidade do tipo tardio (HTT), confirmando o padrão de resposta desviado para um perfil Th1. A análise histológica dos órgãos dos camundongos IL-10 KO revelou ausência de granulomas e fungos no pulmão em contraste aos seus controles WT que apresentavam elevado número de granulomas e fungos neste órgão. A análise dos linfócitos infiltrantes nos pulmões dos camundongos IL-10 KO mostrou redução na frequência de células B, o que é coerente com a baixa síntese de anticorpos observada. Houve aumento marcante na freqüência de células T CD4+ e T CD8+ memória/efetora, caracterizando mais uma vez a eficiente resposta imune celular nesses animais associada à ausência do papel regulador negativo da IL-10. Em fase mais tardia (16 semanas pós-infecção) a regressão da infecção nos camundongos IL-10 KO continuou evidente pelo pequeno número de fungos recuperados do pulmão, acompanhada de baixa síntese de citocinas (IL-5 e IL-2) e de anticorpos anti- P. brasiliensis. Na 23ª semana de infecção além da baixa carga fúngica nos camundongos IL-10 KO, associada à baixa frequência de células responsáveis pela imunidade celular ocorreu também redução na freqüência de células Treg, indicando o papel regulador da IL-10 nesta subpopulação celular. A elevada sobrevida (90%) dos animais IL-10 KO foi coerente com a baixa carga fúngica e eficiente resposta imune no curso da infecção. Em conjunto, nosso trabalho demonstra o importante papel regulador da IL-10 na imunidade da PCM.Cellular immunity is the main defense mechanism of hosts infected by the Paracoccidioide brasiliensis (Pb), a dimorphic fungus that causes the most important systemic mycosis in Latin America. IFN-g activated macrophages participate in this activity that is antagonized by IL-10 an anti-inflammatory cytokine. Both, in the human pathology and in experimental models, there are a number of evidences indicating that IL-10 acts as a suppressor of cellular immunity leading to deleterious effects to the hosts. However, direct studies aimed at investigating the function of IL-10 in the immunity to paracoccidioidomycosis (PCM) have not been performed. Thus, the fundamental objective of this work was to study the function of IL-10 in the mechanisms of innate and adaptive immunity against Pb using as experimental model IL-10 deficient mice (IL-10 Knockout, IL-10 KO) compared to their respective wild type (WT) controls. We demonstrated in vitro that normal peritoneal macrophages of IL-10 KO mice presented increased phagocytic and microbicidal activities than macrophages of WT mice and this was associated witch an elevated production of IFN-g, TNF-α, nitric oxide (NO) and the chemokine MCP-1. However, the production of IFN-g seen to be performed by NTK cells contaminating adherent macrophages, suggesting a possible participation of these cells in the activation of macrophages and T cells of IL-10 KO mice. In vivo studies revealed that at the second week of infection IL-10 KO mice presented an earlier immune response when compared to wild-type mice, since their lungs exhibited a significantly reduced fungal burden and an increased production of almost all antibodies isotypes (IgM, IgG1, IgGM, IgG2b). This effect was accompanied by a total absence of IL-4 and IL-5, showing a regulatory action of IL-10 in the synthesis of Th2 cytokines. Four weeks post-infection, the fungal load was still lower in the IL-10 KO mice but no differences in antibody synthesis was observed. However, the analysis of lung infiltrating leukocytes revealed an increased frequency of TCD4+ and TCD4+CD44 high lymphocytes in IL-10 KO mice, again demonstrating an early activation of cellular immunity in IL-10 KO mice. When compared with WT mice, the pulmonary fungal loads of IL-10 KO mice at week 8 of infection were drastically reduced and no dissemination to other organs were observed. The histopathological analysis revealed an absence of granulomas and fungi in the lungs of IL-10 KO in comparison with WT mice. The analysis of lung infiltrating leukocytes showed that IL-10 KO mice had a reduction in the frequency of B cells, in agreement with the reduced synthesis of immunoglobulins. An increased frequency of activated T CD4+ and a drastic increase of TCD4+ and T CD8+ effector/memory cells charactering once again an efficient immune response associated with IL-10 deficiency. In later stages, sixteen weeks after infection, a regressive infection of IL-10 KO mice was further characterized by low numbers of fungi in the lung, reduced synthesis of cytokines (IL-4 and IL-5) and anti- P. brasiliensis antibodies. By week 23 after infection, in addition to the characteristic reduction of fungal loads and reduced frequency of immune cells, we observed a decrease in the frequency of Treg cells, demonstrating the implication of IL-10 in the control of this T cell population. The elevated survival (90%) of IL-10 KO mice was in total agreement with the low fungal burdens and efficient immune response observed during infection. In conclusion, our work demonstrates for the first time that IL-10 plays a major role in the control of innate and adaptive immunity to Pb infection.
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Cirocco, Robert E. "Cytokine analisys in atlantic bottlenose dolphins: molecular characterization of IL-4, IL-6, and IL-10." FIU Digital Commons, 2001. http://digitalcommons.fiu.edu/etd/2370.
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The health status of wild and captive Atlantic Bottlenose dolphins (Tersiops truncatis) is difficult to ascertain. Mass strandings of these animals have been attributed to pollutants, as well as bacterial infections. Using human Enzyme Linked Immuno-Assays (ELISA) for immunological cytokines, I measured soluble cytokine levels with respect to their health status. In a retrospective analysis of dolphin sera, there was a trend of higher cytokine levels in “sick” animals. I cultured dolphin lymphocytes in the presence of a mitogen (PHA), a super antigen (Staph-A), Lipopolysaccharide (LPS), and a calcium flux inducer (PMA). Levels of messenger RNA, from these cultured cells, were assayed with Polymerase Chain Reaction (PCR) using primers for the human cytokines IL-2, EL-4, IL- 6, IL-10, Tumor Necrosis Factor, and Interferon gamma. Only IL-4, IL-6, and IL-10 messages were obtained, inferring similar nucleotide homology to the human primer sequences. The PCR products were sequenced. Sixteen IL-4 sequences, twelve IL-6 sequences and seven IL-10 sequences were obtained and analyzed. Each cytokine exhibited the same nucleotide sequence in all dolphins examined. There was no difference in the cytokine profile in response to the various stimuli. The derived amino acid composition for each of the dolphin cytokines was used for molecular modeling, which showed that dolphin IL-4, IL-6, and IL-10 were structurally similar to the corresponding proteins of Perissodactyla.
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Mitchell, Ruth Elizabeth. "Regulation of IL-10 in CD4+ T cells." Thesis, University of Bristol, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.691167.
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OLIVEIRA, Gabriela Almeida de. "Polimorfismos de citocinas (TNF-A, IL-10 e IL-17) no câncer gástrico." Universidade Federal do Pará, 2016. http://repositorio.ufpa.br/jspui/handle/2011/7251.
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No Norte do Brasil, o câncer gástrico (GC) é a segunda neoplasia mais frequente entre os homens e o terceiro nas mulheres, portanto, um importante problema de saúde pública. A investigação de fatores genéticos relacionados com características imunológicas pode auxiliar o entendimento da carcinogênese no CG. O objetivo do presente trabalho foi polimorfismos presentes nos genes das interleucinas IL17G-197A, IL 17FA7488G, TNFαG-308A, IL10G- 1082A, IL10C-819T e IL10C-592A, em amostras de pacientes com câncer gástrico e sem câncer. O grupo caso foi composto por 100 pacientes diagnosticados com CG, atendidos no Hospital HUJBB (Pará, Brasil). O grupo controle foi constituído de 100 indivíduos, não aparentados, sem câncer da mesma população. O material genético foi extraído a partir de 5 mL de sangue periférico pelo kit comercial de DNA da Roche, seguido de quantificação com o NanoDrop 1000 spectrophotometer. Molecular analysis of the polymorphisms was performed by real-time PCR with TaqMan® probes. E as medidas de ancestralidade foram investigadas utilizando um painel de 48 marcadores autossômicos informativos de ancestralidade (AIMs). As proporções de ancestralidade de Europeu, Africano e Ameríndio foram estimadas usando o software STRUCTURE v.2.3.3. Como resultado, observou-se que a composição étnica do grupo com câncer foi de 27% africano, 42% europeu, e 31% de ameríndia. No grupo sem câncer, a composição foi de 21 % africano, 52% europeia, e 27% de ameríndia. Em relação ao conjunto de marcadores da interleucina IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A), quando comparados os padrões genotípicos e haplotípicos observou-se que a distribuição haplotípica, quando relacionada a elevada expressão (GCC/GCC, GCC/GCA, GCC/GTC, GCA/GCA, GCA/GTA) foi mais frequente no grupo de pacientes com câncer gástrico (p=1,15E-11; OR=2,630; IC 95%=2,116-3,271). Em indivíduos que possuíam o genótipo relacionado com a elevada produção de IL-10, detectou-se maior frequência da ancestralidade europeia no grupo de indivíduos controle (p=1E-06), enquanto no grupo de pacientes com CG observou significante frequência da ancestralidade africana (p=1.4 e-5), pacientes que apresentaram genótipos TNF-α AA e TNF-α AG para mutação no gene TNF-α, apresentam risco elevado para desenvolvimento do câncer (P <000.1; OR 10.375; IC 95% 3.149- 34.061). Concluimos que a distribuição haplotípica dos marcadores da interleucina IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A) quando relacionados a elevada expressão e predominância de ancestralidade africana, possuem maior risco de desenvolvimento do CG.
Gastric cancer (GC) is the second most common malignancy among men and the third in women, and therefore, an important public health problem in northern Brazil. The investigation of genetic factors related to immunological characteristics can aid the understanding of carcinogenesis in CG. The objective of the present work was investigate polymorphisms present in interleukin genes IL17G-197A, IL 17FA7488G, TNFαG-308A, IL10G-1082A, IL10C-819T e IL10C-592A, on samples of patients with gastric cancer and healthy patients without cancer. Case group was composed of 100 patients diagnosed with CG, met in the Hospital HUJBB (Pará, Brazil). Control group was composed of 100 individuals without cancer, unrelated, of the same population. The genetic material was extracted from 5 mL of peripheral blood with the DNA commercial kit from Roche, followed by quantification with the NanoDrop 1000 spectrophotometer. Analysis of the molecular polymorphisms was performed by real-time PCR with Taqman® probes. Measures of ancestry were investigated using a panel of 48 autosomal ancestry informative markers (AIMs). The proportions of ancestry of European, African and Amerindian were estimated using the software STRUCTURE v. 2.3.3. It was observed that the ethnic composition of the case group was 27% African, 42% European and 31% of Amerindian, while in the control group 21% African, 52% of European and 27% of Amerindian. In relation to the set of markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A), when the genotypic and haplotypic patterns were compared, it was noted that the haplotype distribution related to high expression (GCC/GCC, GCA, GCC/GCC/GTC, GCA/GCA, GCA/GTA) was more frequent in the patients with gastric cancer (P = 1,15e-11; OR = 2.630; IC 95% = 2.116-3.271). Among the individuals with the genotype related to the high production of IL-10, it was observed that the control group had more European contribution in their ancestry (P = 1e-06) while the group of patients with CG had more African contribution in their ancestry (P = 1.4e-5). Patients who presented TNF-α AA and TNF-α AG genotypes for TNF-α gene mutation presented a higher risk for development of cancer (P<0.001; OR 10.375; IC 95% 3.149-34.061). It is concluded that patients with a distribution of haplotypic markers of interleukin IL-10 (IL10G-1082A, IL10C-819T, IL10C-592A) related to a higher expression and higher contribution of African ancestry have a high risk of developing gastric cancer.
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Beigel, Florian. "Die Bedeutung der IL-10-verwandten Zytokine IL-22, IL-28A und IL-29 bei intestinaler Entzündung und viraler Infektion." Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-80038.
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OLIVEIRA, Jacqueline Flores de. "Níveis séricos de interleucinas IL-6 e IL-10 em indivíduos com transtorno de estresse pós-traumático em uma amostra de base populacional." Universidade Catolica de Pelotas, 2018. http://tede.ucpel.edu.br:8080/jspui/handle/jspui/691.
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Post-traumatic stress disorder (PTSD) is a psychiatric disorder with a prevalence of 8% in the population throughout life. Recent studies have suggested that in PTSD there is the activation of the immune system with the increase of inflammatory mediators, being able to influence the affective behavior and development of comorbidities. Thus, this study aimed to evaluate the serum levels of interleukins IL-6 and IL-10 in individuals with PTSD in a population-based sample. This is a case-control study, nested in a populationbased cross-sectional study involving 82 individuals aged 18-35 years living in the urban area of the city of Pelotas / RS. All individuals diagnosed with PTSD were selected, who were not diagnosed with major depressive disorder (MDD), did not report use of psychiatric and anti-inflammatory medications, constituting a group of 41 individuals. Of these, 41 other individuals with the same clinical characteristics of the previous group, differentiated only because they did not have PTSD diagnosis, were matched by sex and age, constituting a control group. Data were collected through a self-administered questionnaire with sociodemographic questions and psychoactive substance use. The Mini International Neuropsychiatric Interview was used for the diagnosis of PTSD and MDD. After the interview, 10 mL of blood was collected. Serum levels of IL-6 and IL10 were measured by the ELISA technique using commercial kits. The group of individuals with PTSD presented a statistically significant increase in the serum levels of the pro-inflammatory cytokine IL-6 and anti-inflammatory IL-10 (p = 0.002) when compared to the control group. The results presented here suggest that individuals with PTSD may present an activation of the immune system and may be related to a neuroinflammatory process and the development of several clinical complications.
O transtorno de estresse pós-traumático (TEPT) é um transtorno psiquiátrico com uma prevalência de 8% na população ao longo da vida. Estudos recentes têm sugerido que no TEPT há a ativação do sistema imune com o aumento de mediadores inflamatórios, podendo influenciar no comportamento afetivo e desenvolvimento de comorbidades. Assim, este estudo teve como objetivo avaliar os níveis séricos das interleucinas IL-6 e IL-10 em indivíduos com TEPT em uma amostra de base populacional. Trata-se de um estudo de caso-controle aninhado a um estudo transversal de base populacional, envolvendo 82 indivíduos de 18 a 35 anos, residentes na zona urbana da cidade de Pelotas/RS. Foram selecionados todos os indivíduos diagnosticados com TEPT, os quais não foram diagnosticados com transtorno depressivo maior (TDM), não relataram uso de medicações psiquiátricas e anti-inflamatórias, constituindo um grupo de 41 indivíduos. Destes, outros 41 indivíduos com as mesmas características clínicas do grupo anterior, diferenciado apenas por não ter diagnóstico de TEPT, foram pareados por sexo e idade, constituindo um grupo controle. Os dados foram coletados através de um questionário autoaplicável com questões sociodemográficas e usos de substâncias psicoativas. Para o diagnóstico de TEPT e TDM foi utilizado o Mini International Neuropsychiatric Interview. Após a entrevista foram coletados 10 mL de sangue. Os níveis séricos de IL - 6 e IL-10 foram mensurados através da técnica de ELISA, utilizando kits comerciais. O grupo de indivíduos com TEPT apresentou um aumento estatisticamente significativo nos níveis séricos da citocina pró-inflamatória IL-6 e anti-inflamatória IL-10 (p=0.002) quando comparados ao grupo de indivíduos controle. Os resultados aqui apresentados sugerem que indivíduos com TEPT podem apresentar uma ativação do sistema imunológico, podendo estar relacionado com um processo a neuroinflamatório e o desenvolvimento de diversas complicações clínicas.
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Shoemaker, John. "Molecular mechanisms for the regulation of the Il-10 gene in CD4 T cells : comparison of IL-10-Treg and CD25+Treg." Thesis, Open University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.427840.
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Assrafally, Farryah. "Modulation of pathological cardiac hypertrophy via the interleukin-10 signalling in the cardiomyocytes." Thesis, University of Manchester, 2016. https://www.research.manchester.ac.uk/portal/en/theses/modulation-of-pathological-cardiac-hypertrophy-via-the-interleukin10-signalling-in-the-cardiomyocytes(430247dd-1512-4e29-9f7a-288bae85fffd).html.
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Inflammation plays a key role during pathological hypertrophy and heart failure. Whilst the roles of pro-inflammatory cytokines are relatively well understood, little is known about the anti-inflammatory cytokines in the heart. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role during cardiac remodelling. IL-10 exerts its function by binding to the IL-10 receptor (IL-10R). The primary aim of the PhD study was to investigate the effects of the ubiquitous ablation of IL-10R1 gene during pressure overload induced hypertrophy and to characterise the downstream pathway regulated by IL-10R1 in the heart following pressure overload. The second aim was to investigate the effects of cell specific ablation of IL-10R1 in both the macrophages and cardiomyocytes during pressure overload induced hypertrophy and to identify the specific site where IL-10R1 regulates hypertrophy in the heart. During this study three mouse lines were used: IL-10R1 global knockout (IL-10R1-/-), IL-10R1 macrophage-specific knockout (IL-10R1mKO) and IL-10R1 cardiomyocyte-specific knockout (IL-10R1cKO).Mice with systemic ablation of IL-10 receptor1 (IL-10R1-/-) displayed a significant increase in hypertrophy following two weeks of transverse aortic constriction (TAC) as indicated by heart weight/tibia length ratio (HW/TL). This was accompanied by a significant increase in cardiomyocyte surface area as well as expression of hypertrophic markers such as brain natriuretic peptide (BNP) and Atrial natriuretic peptide (ANP). The IL-10R1-/- mice also had a significant increase in cardiac fibrosis when compared to the WT TAC littermates. Importantly, ejection fraction (EF) and fractional shortening (FS) were significantly reduced in IL-10R1-/- mice compared with WT littermates following TAC. The STAT3 pathway is known as the major downstream signalling pathway regulated by the IL-10R via the activation of the JAK1/STAT3 pathway. Western blot analysis showed that activation of the STAT3 signalling pathway was significantly reduced in IL-10R1-/- mice following TAC, indicating the possible involvement of this pathway. Furthermore, expression of STAT3 target genes: suppressor of cytokine signalling (SOCS3), tissue inhibitor of metalloproteinases3 (TIMP-3) and heme oxygenase (HO-1) were downregulated in the IL-10R1-/- mice following TAC. Overall the data obtain from the IL-10R1-/- mice indicate that IL-10R1 signalling plays a protective role in reducing pathological hypertrophy in the heart. Interestingly, IL-10R1mKO mice showed no difference in the hypertrophic response following TAC. Analysis of cardiac function and STAT3 activation also showed no difference between IL-10R1mKO and WT controls. This indicated that the protective effects of IL-10R1 mediated signalling during cardiac pressure overload was unlikely due to the effects in residential macrophages. In contrast, IL-10R1cKO mice displayed an elevated hypertrophic response, reduction of cardiac function and less STAT3 activation after TAC. This phenotype resembled those of IL-10R1 global knockout mice. In conclusion, this PhD study has shown that IL-10R1 mediated signalling in the heart is important in controlling pressure-overload hypertrophy. Using cell-specific knockout mice I have shown that IL-10R signalling in cardiomyocytes and not in macrophages is important in this process. These results will open a new insight in targeting IL-10 receptor in the treatment of myocardial hypertrophy in future.
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Pathania, Uday Singh. "Cloning and characterisation of the chicken IL-10 family." Thesis, Royal Veterinary College (University of London), 2008. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522707.
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Ghanipour, Ali. "IL-10 regulates macrophage activation through activation of SHIP." Thesis, University of British Columbia, 2007. http://hdl.handle.net/2429/30873.
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IL-10 is a potent anti-inflammatory and immunosuppressive cytokine, which
regulates macrophages by activation of the STAT3 pathway. However, several lines of
evidence suggest that IL-10 can inhibit macrophage activation independent of STAT3
through currently unknown mechanisms and pathways. Here for the first time, we show
that in murine macrophages, IL-10 activates Src Homology 2 Domain-containing Inositol
5'-Phosphatase (SHIP), a molecule with reported anti-inflammatory effects. Activation
of SHIP by IL-10 is required for inhibition of Tumor necrosis factor alpha (TNFα) in
macrophages. Additional experiments revealed that IL-10 activation of SHIP acted at the
post-transcriptional level and inhibited translation of TNFα . Using a novel small
molecule activator of SHIP, AQX-016A, we further confirmed that activation of SHIP
alone could inhibit TNFα translation.
IL-10 activation of SHIP results in the inhibition of the LPS induced increase in
the PI3K product, PIP3, at the membrane. However, conflicting data as to the role of
PI3K in regulation of TNFα have been presented. Our studies show that PI3K inhibition
downregulates TNFα production in peritoneal and several other macrophage lines, and
upregulates it bone marrow derived macrophages (BMDM). Interestingly, this difference
is due to the increased amount of autocrine negative regulators produced in BMDM,
removal of which exposes the positive role PI3K plays in regulation of TNFα. Therefore,
our studies confirm that PI3K activity positively regulates TNFα production in
macrophages and that inhibition of TNFα by IL-10 or AQX-016A through activation of
SHIP is likely due to SHIP'S ability to antagonize this pathway. The importance of this pathway is further highlighted as IL-10 inhibition of LPS-induced septic shock in mice
lacking one allele of SHIP is significantly attenuated. Furthermore, activation of SHIP
by AQX-016A inhibits TNFα production in septic mice.
We also found that IL-10 inhibited LPS induced p38 activity in a cell-dependent
manner. However in all cells tested, IL-10 activated p38 rapidly. We identified several
IL-10 induced genes including CRIM1, a transmembrane protein with no previous report
of involvement in the immune system. We found that IL-10 induction of CRIM1 was
partly dependent on the activity of p38. However, expression of CRIM1 does not seem
to be involved in the anti-inflammatory effects of IL-10.Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
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Perona-Wright, Georgia. "The influence of IL-10 on dendritic cell activation." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/25073.
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Dendritic cells (DCs) are the watchmen of the immune system. They survey the peripheral tissues and display samples of surrounding antigens for inspection by T cells. Pathogenic or inflammatory signals trigger DCs to mature, upregulating their expression of MHC and costimulatory molecules and converting them into potent T cell stimulators. The character of the activated DC depends not only on the stimulus but also on concomitant environmental signals. This thesis tests the hypothesis that in vitro manipulation of DC function can be used to direct immune responses in vivo. The work focuses on the cytokine IL-10 and asks whether its impact on DC maturation can mediate T cell tolerance. IL-10 has been reported to trap DCs in an immature state, leading to antigen presentation without full costimulation and consequent T cell anergy. Data presented here show that DCs do become activated in the presence of IL-10. They downregulate antigen uptake and, 6 hours after stimulation, display high levels of MHCII and B7. Their activation is short-lived, with both MHC and B7 expression returning to baseline within 18h. Even at 6 hours, with high levels of surface MHC and costimulation, the IL-10 treated DCs express little 1L-12 and fail to elicit strong T cell proliferation. IL-10 seems not to act by inhibiting DC maturation but instead by dictating the kinetics and quality of their activation. The consequence of this DC activation for the responding T cells is also examined. Both in vitro and in vivo, using co-cultures and adoptive transfers of TCR transgenic T cells followed by DC-based immunisation, initial contact with IL-10 treated DCs appears to leave T cells hyporesponsive to subsequent challenge. In a mouse model of autoimmunity, these DCs suppress disease. Taken together these data suggest that, rather than preventing DC maturation, IL-10 directs an active DC phenotype that can regulate immune responses. These DCs have exciting therapeutic potential.
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SERAFINI, GIORGIA. "IL-10 mediated immunological tolerance: preclinical and clinical studies." Doctoral thesis, Università degli Studi di Roma "Tor Vergata", 2009. http://hdl.handle.net/2108/1022.
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Thalassemia Major can be cured with allogeneic hematopoietic stem-cell transplantation (HSCT). Persistent mixed chimerism (PMC) develops in around 10% of transplanted thalassemic patients, but the biological mechanisms underlying this phenomenon are poorly understood. IL-10 is an immunomodulant cytokine that plays a central role in controlling inflammation, down-regulating immune responses, and inducing immunological tolerance. Detection of high levels of IL-10, produced by PBMCs of patients with PMC, in comparison to those of patients with complete donor chimerism (CC) or normal donors (ND), prompted us to characterize the T cell repertoire in a thalassemic patient with long-term tolerance following HSCT. From the peripheral blood of the PMC patient, T cell clones of both host and donor origin could be isolated. Together with effector T cell clones, reactive against host or donor alloantigens, we identified regulatory T cell clones, with a cytokine secretion profile typical of type 1 regulatory T cells (Tr1), at high frequencies. Tr1 cell clones, both donor and host derived, were able to inhibit the function of effector T cells of either donor or host origin in vitro, suggesting a contribution by these regulatory T cells to the maintenance of PMC in vivo.
In parallel, we demonstrated that IL-10 could inhibit primary allogeneic proliferation of total PBMCs and could induce antigen-specific T-cell hyporesponsiveness. The use of tolerogenic dendritic cells (DC) differentiated in the presence of IL-10 (DC-10), as compared to monocytes+IL-10, allowed a more consistent anergy induction, even in the context of HLA-matched donors. Importantly, both monocytes+IL-10-anergized and DC-10-anergized T cells preserved their ability to respond to nominal and third party antigens.
All together these results provide first, new insights regarding the mechanisms of peripheral tolerance in transplanted thalassemic patients, and secondly, offer a strong rationale for the development of a clinical protocol for the use of ex-vivo monocytes+ IL-10/DC-10-anergized T cells of donor origin as cellular therapy to promote immune-reconstitution and prevent graft-versus-host disease after HSCT.
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Vilela, Josie Fadul 1982. "Investigação dos polimorfismos dos genes da interleucina-1 (IL-1), IL1RN, IL-4, IL-6 e IL-10 em pacientes adultos portadores de púrpura trombocitopênica imune = Investigation of interleukin-1 (IL-1), IL1RN, IL-4, IL-6 and IL-10 gene polymorphism adult patients with immune thrombocytopenic purpura." [s.n.], 2012. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310653.
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Orientador: Marcelo Addas CarvalhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: A Púrpura Trombocitopênica Imune (PTI) é uma doença autoimune caracterizada pela presença de autoanticorpos contra as glicoproteínas de membrana plaquetária, tais como GPIIb/IIIa e GPIb/IX. O processo patogênico da PTI envolve uma destruição acelerada das plaquetas pelo sistema retículo-endotelial e a presença de sangramentos mucocutâneos. A reação inflamatória em doenças infecciosas e autoimune é regulada por um balanço entre as citocinas pró e anti-inflamatórias e a PTI tem sido associada com a desregulação das respostas e atividades de citocinas. Uma associação entre os polimorfismos de genes de citocinas que afetam sua produção e secreção foram relatadas em doenças infecciosas, alérgicas, autoimunes, e malignas, tanto na fase de formação quanto no decurso da doença e nas suas respostas ao tratamento. Neste estudo, o objetivo foi avaliar a importância dos polimorfismos IL1B -511C/T, IL1B +3953C/T, IL1RN intron 2 VNTR, IL4 -590C/T, IL4 intron 3 VNTR, IL6 -174G/C, IL10 -1082G/A, IL10 -819C/T e IL10 -592 A/C em pacientes portadores de PTI na região de Campinas, SP e investigar a associação entre os genótipos identificados e a resposta clínica do paciente ao tratamento. Utilizamos o método PCR e digestão com enzima de restrição (PCR-RFLP) ou PCR em Tempo real (RT-PCR) para identificação dos polimorfismos. No total, 216 pacientes adultos diagnosticados com PTI foram pareados com 119 controles saudáveis constituídos por doadores voluntários do Centro de Hematologia e Hemoterapia da UNICAMP. Os dados clínicos como contagem de plaquetas ao diagnóstico, tipo de tratamento e resposta, foram obtidos através dos prontuários médicos. A análise de frequências dos alelos e genótipos dos polimorfismos IL1B - 511C/T, IL1B +3953C/T, IL6 -174G/C, IL10-1082G/A, IL10 -819C/T e IL10 -592A/C de pacientes portadores de PTI comparadas ao grupo controle não mostrou diferenças significativas entre os dois grupos. No entanto, para os polimorfismos IL1RN intron 2 VNTR, IL4 -590C/T, IL4 intron 3 VNTR e para os haplótipos de IL10 houve uma diferença significativa ao compararmos as frequências polimórficas entre os dois grupos. Analisando-se os polimorfismos associados com parâmetros clínicos, este estudo mostrou que o genótipo IL1B -511CC estava mais presente em indivíduos com boa resposta à esplenectomia. Pode-se concluir que o estudo de características genéticas dos pacientes portadores de PTI na região de Campinas, SP pode ajudar a esclarecer o perfil de pacientes acometidos pela doença nesta região, identificando grupos de maior risco e a entender qual polimorfismo pode estar associado a uma melhor resposta clínica, projetando uma nova linha de investigação
Abstract: The immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by the presence of autoantibodies against the platelet membrane glycoproteins such as GPIIb/IIIa and GPIb/IX. The pathogenic process of ITP involves an accelerated destruction of platelets by reticuloendothelial system and the presence of mucocutaneous bleeding. The inflammatory reaction in infectious and autoimmune diseases is regulated by a balance between pro and anti-inflammatory cytokines and ITP has been associated with dysregulation of cytokine responses and activities. An association between cytokine gene polymorphisms that affect their production and secretion have been reported in infectious, allergic, autoimmune, and malignant diseases, both during training and during the illness and its response to treatment. The aim of this study was to evaluate the importance of IL1B -511C/T, IL1B +3953 C/T, IL1RN intron 2 VNTR, IL4 -590C/T IL4 intron 3 VNTR, IL6 -174G/C, IL10 -1082G/A, IL10 -819C/T and IL10 -592A/C polymorphisms in patients with ITP in the region of Campinas, SP, and investigate the association between different genotypes and clinical responses to treatment. We used the PCR method and digestion with restriction enzyme (PCR-RFLP) or real-time PCR (RT-PCR) to identify polymorphisms. In total, 216 adult patients diagnosed with ITP were matched with 118 healthy controls. The clinical data such as platelet count at diagnosis, type of treatment and response were obtained from medical records. Analysis of allele and genotypes frequencies of IL1B -511C/T, IL1B +3953C/T, IL6 -174G/C, IL10 - 1082G/A, IL10 -819C/T and IL10 -592A/C polymorphisms in patients with ITP compared to the control group showed no significant differences between the two groups. However, for IL1RN intron 2 VNTR polymorphisms, IL4 -590C/T, IL4 intron 3 VNTR and IL10 haplotypes there were a significant difference when comparing polymorphic frequencies between the two groups. Analyzing the polymorphisms associated with clinical parameters, this study showed that IL1B -511CC genotype was more frequent in individuals with good response to splenectomy. It can be concluded that the study of genetic characteristics of patients with ITP in the region of Campinas, SP should help clarify the profile of patients affected, identifying groups at higher risk and understanding which polymorphism may be associated with better clinical response
Mestrado
Clinica Medica
Mestra em Clínica Médica
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Lombard, Robin. "Rôle des polynucléaires neutrophiles dans la régulation de la réponse inflammatoire IL-17A lors de l'infection pulmonaire par les mycobactéries." Thesis, Tours, 2013. http://www.theses.fr/2013TOUR4048/document.
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La pandémie de tuberculose (TB) causée par Mycobactérium tuberculosis (Mtb) n’est pas contrôlée par le vaccin vivant BCG. Mtb induit la formation de granulomes qui évoluent vers une réaction inflammatoire exacerbée détruisant le poumon lors de la TB active. Les rôles des polynucléaires neutrophiles (PNN) et de la cytokine inflammatoire IL-17A dans cette évolution sont à clarifier. Nous montrons, chez la souris, que les PNN sont recrutés dans le poumon en deux vagues après infection par Mtb ou BCG. La deuxième vague dépend du récepteur IL-17RA exprimé par les cellules non-hématopoïétiques. Les chimiokines CXCL-1 et 5 attirant les PNN semblent impliquées. Dans le poumon, ces PNN produisent la cytokine immunosuppressive IL-10 qui diminue la production d’IL-17A. Les cellules dendritiques infectées, présentes dans le granulome, sécrètent aussi CXCL-1. Elles attirent les PNN qui produisent de l’IL-10 bloquant la production d’IL-17A mais pas d’IFN-γ. En effet, seuls les lymphocytes CD4+ Th17 expriment le récepteur à l’IL-10. Nos travaux apportent un éclairage nouveau sur les PNN régulateurs dans le contrôle de inflammation due à l’IL-17A lors de la TBTuberculosis (TB) pandemic, caused by Mycobacterium tuberculosis (Mtb), is not controlled by the live vaccine BCG. Mtb induces granuloma formation developing to exacerbated inflammation that destroys the lung during active TB. Roles played by polymorphonuclear neutrophils (PMN) and inflammatory cytokine IL-17A remain ill defined. We show, in the mouse model, that PMN reach the lung in two waves following lung infection with BCG or Mtb. Only the second wave depends on receptor IL-17A expression by non hematopoietic cells. PMN chemoattractants CXCL-1 and 5 seem involved in this late recruitment. In the lung PMN produce immunosuppressive IL-10 that dampens IL-17A production. Mycobacteria infected dendritic cells, present inside granuloma, also secrete CXCL-1. Neutrophils attracted towards infected dendritic cells secrete IL-10 that inhibits IL-17A but not IFN-g production. Indeed, CD4+ Th17 and not Th1 express the IL-10 receptor. Our data shed new light on regulatory PMN in IL-17A-driven lung inflammation during TB
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Beigel, Florian [Verfasser]. "Die Bedeutung der IL-10-verwandten Zytokine IL-22, IL-28A und IL-29 bei intestinaler Entzündung und viraler Infektion / Florian Beigel." München : Universitätsbibliothek München, 2008. http://d-nb.info/1006744843/34.
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Піддубна, Анна Іванівна, Анна Ивановна Поддубная, Anna Ivanivna Piddubna, Микола Дмитрович Чемич, Николай Дмитриевич Чемич, and Mykola Dmytrovych Chemych. "Прогностичне значення алельного поліморфізму генів IL-4, IL-10, TNF-α у ВІЛ-інфікованих осіб." Thesis, Укрмедкнига, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32436.
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З’ясовано взаємозв’язок розподілу алельних варіантів генів IL-4, IL-10, TNF-α у ВІЛ-інфікованих пацієнтів з різними типами перебігу інфекційного процесу.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32436Установлена взаимосвязь распределения аллельных вариантов генов IL-4, IL-10, TNF-α у ВИЧ-инфицированных пациентов с различными типами течения инфекционного процесса. При цитировании документа, используйте ссылку http://essuir.sumdu.edu.ua/handle/123456789/32436
It was found the correlation distribution of allelic variants of IL-4, IL-10, TNF-α genes in HIV-infected patients with different types of infection course. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/32436
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Wang, Allen Ping-Lun. "The effect of hypoxia on the production of interleukin-10 (IL-10) in human mononuclear cells." Thesis, University of Leicester, 2010. http://hdl.handle.net/2381/10228.
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Macrophages play an important role in both innate and adaptive immunity by engulfing intruding pathogens and damaged or infected cells, antigen presentation, and by secretion of immune mediators. Interleukin 10 (IL-10) is a potent anti-inflammatory cytokine mainly produced by macrophages in response to cell activation, which serves to suppress immune reactions and inflammation. Hypoxia refers to oxygen deprivation. It is a common condition found in pathological tissues. The relationship between hypoxia and the production of IL-10 by macrophage is not yet thoroughly understood. In previous unpublished work by Staples and Burke et. al., it was found that both basal and LPS-induced IL-10 mRNA and protein are reduced in hypoxia. In the present study, it was shown that the transcription factor Hypoxia Inducible Factor 1 (HIF-1) appears to be involved in this reduction of IL-10 production in hypoxia. Although the regulatory elements on the IL-10 promoter responsible for this blockage effect were not definitively identified, our results indicated that the activity of a -4kb IL-10 luciferase reporter adenovirus was significantly reduced in cells treated with the HIF-1 inducing agents, cobalt chloride and desferrioxamine. The activity of a -195bp IL-10 luciferase reporter adenovirus was also decreased in the HIF-1inducing agent treated samples. These data imply that either by indirect interaction or physically binding to the IL-10 promoter or gene, HIF-1 does play a role in blocking IL-10 expression in hypoxia. Sequence and transcription factor analysis indicated the presence of a HIF-1 consensus sequence hypoxia responsive element (HRE) located in the -2,171bp to -2,187bp position on the IL-10 promoter. This result suggests that HIF-1 may affect IL-10 production, at least in part, by physically binding to its promoter. Lastly, we showed that the effect of hypoxia on IL-10 expression is observed with a range of different toll-like receptor ligands, and is not limited to induction by LPS.
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Піддубна, Анна Іванівна, Анна Ивановна Поддубная, and Anna Ivanivna Piddubna. "Поліморфізм гену IL-10 (-592C/А) у ВІЛ-інфікованих осіб." Thesis, Запорізький державний медичний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/31891.
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Наведені дані щодо розподілу алельних варіантів поліморфізм гену IL-10 (-592C/А) у ВІЛ-інфікованих українців
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/31891Приведенные данные по распределению аллельных вариантов полиморфизм гена IL-10 (-592C/А) у ВИЧ-инфицированных украинцев При цитировании документа, используйте ссылку http://essuir.sumdu.edu.ua/handle/123456789/31891
The data of the distribution of allelic variants IL-10 (-592C/A) gene polymorphismin HIV-positive Ukrainian was presented When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/31891
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Maynard, Craig Lueland. "IL-10-competent regulatory T cells development, phenotype and function /." Thesis, Birmingham, Ala. : University of Alabama at Birmingham, 2007. https://www.mhsl.uab.edu/dt/2009r/maynard.pdf.
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Dokka, Sujatha. "IL-10 gene therapy for the treatment of pulmonary inflammation." Morgantown, W. Va. : [West Virginia University Libraries], 2000. http://etd.wvu.edu/templates/showETD.cfm?recnum=1421.
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Thesis (Ph. D.)--West Virginia University, 2000.Title from document title page. Document formatted into pages; contains ix, 132 p. : ill. (some col.) Vita. Includes abstract. Includes bibliographical references.
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De, Simone Marco <1975>. "Molecular characterization of human CD4+ IL-10-producing regulatory cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6520/1/De_Simone_Marco_tesi.pdf.
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Previous studies in the group led to the identification of CD4+FOXP3- cells with regulatory functions in human blood that coproduce IL-10 and IFN-gamma. These cells do not belong to the Treg cell lineage since they are Foxp3- but they show some similarities with Th1 cells since they express CCR5, T-bet and produce high levels of IFN-gamma. Thus, they share relevant characteristics with both T regulatory type I cells (Tr1) and Th1 cells and we called them Th1-10 cells.
In this study we presented a molecular characterization of Th1-10 cells that includes a gene expression and a microRNA profiling and performed functional studies to assess Th1-10 cells regulatory properties. We demonstrated that Th1-10 cells have a high regulatory potential being able to block the proliferation of activated CD4 naïve T cells to a similar extent as conventional Treg cells, and that this suppression capacity is at least partially mediated by secreted IL10.
We showed also that Th1-10 cells are closely related to Th1 effector memory cells and express genes involved in cytotoxicity. In particular, they express the transcription factor EOMES and the cytotoxic effector molecules GZMA and GZMK, and they release cytotoxic granules upon stimulation. Moreover, we found that Eomes regulates cytotoxic functions in CD4+ T cells.
We demonstrated that miR-92a, selectively downregulated in Th1-10 cells, directly targets the 3’UTR of EOMES.and this finding identifies miR-92a as a possible mediator of Th1-10 cytotoxicity.
Th1-10 cells retain some proliferative capacity when sorted ex vivo and activated in vitro via their TCR, and this effect is markedly enhanced by IL-15, which also had a pro-survival effect on Th-10 cells.
Thus, in contrast to conventional cytotoxic T cells, Th1-10 cells have cytotoxic and regulatory functions and are not terminally differentiated, since they retain proliferative capacity.
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De, Simone Marco <1975>. "Molecular characterization of human CD4+ IL-10-producing regulatory cells." Doctoral thesis, Alma Mater Studiorum - Università di Bologna, 2014. http://amsdottorato.unibo.it/6520/.
Full textAbstract:
Previous studies in the group led to the identification of CD4+FOXP3- cells with regulatory functions in human blood that coproduce IL-10 and IFN-gamma. These cells do not belong to the Treg cell lineage since they are Foxp3- but they show some similarities with Th1 cells since they express CCR5, T-bet and produce high levels of IFN-gamma. Thus, they share relevant characteristics with both T regulatory type I cells (Tr1) and Th1 cells and we called them Th1-10 cells.
In this study we presented a molecular characterization of Th1-10 cells that includes a gene expression and a microRNA profiling and performed functional studies to assess Th1-10 cells regulatory properties. We demonstrated that Th1-10 cells have a high regulatory potential being able to block the proliferation of activated CD4 naïve T cells to a similar extent as conventional Treg cells, and that this suppression capacity is at least partially mediated by secreted IL10.
We showed also that Th1-10 cells are closely related to Th1 effector memory cells and express genes involved in cytotoxicity. In particular, they express the transcription factor EOMES and the cytotoxic effector molecules GZMA and GZMK, and they release cytotoxic granules upon stimulation. Moreover, we found that Eomes regulates cytotoxic functions in CD4+ T cells.
We demonstrated that miR-92a, selectively downregulated in Th1-10 cells, directly targets the 3’UTR of EOMES.and this finding identifies miR-92a as a possible mediator of Th1-10 cytotoxicity.
Th1-10 cells retain some proliferative capacity when sorted ex vivo and activated in vitro via their TCR, and this effect is markedly enhanced by IL-15, which also had a pro-survival effect on Th-10 cells.
Thus, in contrast to conventional cytotoxic T cells, Th1-10 cells have cytotoxic and regulatory functions and are not terminally differentiated, since they retain proliferative capacity.
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Specht, Sabine. "Antagonism between IL-4 and IL-10 in colitis and a helminth infection in Mus musculus." [S.l.] : [s.n.], 2005. http://deposit.ddb.de/cgi-bin/dokserv?idn=975502085.
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SANTOS, Raphaela Silva Leandro. "Avaliação da expressão de CD4, CD25, IL-10, IL-17 E FOXP 3 em cistos radiculares." Universidade Federal de Pernambuco, 2015. https://repositorio.ufpe.br/handle/123456789/25390.
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Made available in DSpace on 2018-08-03T21:59:14Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TESE Raphaela Silva Leandro Santos.pdf: 2858553 bytes, checksum: fed89296295c51fb6999d3c552b880f5 (MD5) Previous issue date: 2015-08-31
Introdução: Pouco se sabe sobre o papel modulador exercido pelos linfócitos T reguladores (Treg) e pelas diferentes citocinas envolvidas no desenvolvimento e manutenção dos cistos radiculares (CR). Diante disso, o objetivo deste estudo foi avaliar a imuno-expressão dos marcadores CD4, CD25, interleucina-10 (IL-10), interleucina -17 (IL-17) e forkhead box P3 (FoxP3) em CR e associar esses achados com características histológicas dessas lesões. Métodos: Cinquenta e cinco espécimes teciduais de CR foram analisados quanto às suas características histológicas e submetidos à análise imuno-histoquímica utilizando os anticorpos anti-CD4, anti-CD25, anti IL-10, anti-IL-17 and anti-FoxP3. Os resultados da imunoexpressão foram correlacionados com a intensidade do infiltrado inflamatório e a espessura do revestimento epitelial cístico. Resultados: Todos os casos apresentaram marcação positiva para todos os marcadores estudados, mas com intensidades de expressão diferentes. A expressão de CD4, CD25, IL-10 e FoxP3 foi considerada fraca para todos os casos avaliados, enquanto que a IL-17 apresentou expressão forte e foi observada tanto nas células inflamatórias quanto no revestimento epitelial. Não foi observada diferença estatisticamente significante entre os marcadores avaliados e a intensidade do infiltrado inflamatório e a espessura do revestimento epitelial. Foi observada correlação positiva as marcações de IL-17 e FoxP3. Conclusão: Os presentes resultados evidenciaram uma participação menos expressiva de células Treg em cistos radiculares, através da fraca expressão de CD4, CD25, IL-10 e FoxP3, em detrimento de uma presença mais significativa de IL-17.
Introduction: Little is known about T regulatory (Treg) lymphocytes and cytokines modulation in development and maintenance of radicular cysts (RC). In this perspective, the aim of this study was to evaluate immunoexpression of the markers CD4, CD25, interleukin-17 (IL-17) and interleukin-10 (IL-10) and forkhead box P3 (FoxP3) in RC and to correlate these findings with the histological features of these lesions. Methods: Fifty five RC tissue specimens were analyzed for their histological characteristics and submitted to immunohistochemical analysis using anti-CD4, anti-CD25, anti IL-10, anti-IL-17 and anti-FoxP3 antibodies. The results of immunoexpression were correlated with the intensity of the inflammatory infiltrate and thickness of the epithelial lining. Results: All cases were positive to all studied markers, but with different expression intensity. The immunoexpression of CD4, CD25, IL-10 and FoxP3 was weak for all evaluated cases, whereas IL-17 exhibited strong expression in all cases. In addition, IL-17 was expressed in both inflammatory and epithelial cells of cystic lining. No significant differences in the number of positive cells were observed in terms of the intensity of the inflammatory infiltrate or epithelial thickness. It was observed positive correlations between the immunoexpressions of IL- 17 and FoxP3. Conclusion: The present results showed a less expressive participation of Treg cells in radicular cysts due to weak expression of CD4, CD25, IL-10 and FoxP3 in detriment to a more significant presence of IL-17.
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Oliveira, Walker Nonato Ferreira. "Regulação da resposta inflamatória na leishmaniose tegumentar: papel de il-10, tgf-β e il-27." reponame:Repositório Institucional da UFBA, 2013. http://www.repositorio.ufba.br/ri/handle/ri/12178.
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NIH Grant; CAPES
Introdução: A forte resposta do tipo Th1, com produção exagerada de IFN- e TNF-α, observada na leishmaniose tegumentar humana causada por Leishmania braziliensis está associada com a destruição tecidual e desenvolvimento de lesão observada em pacientes com leishmaniose cutânea (LC) e em pacientes com leishmaniose mucosa (LM). Em contraste com essas formas clínicas, 10% dos indivíduos residentes em área endêmica, apesar de apresentarem reação de hipersensibilidade tardia para o antígeno de Leishmania, não apresentam evidências de doença clínica e são considerados como tendo a forma subclínica (SC) da doença. A produção de IFN-γ e TNF-α nestes indivíduos é menor quando comparada com pacientes com LC. Existem várias evidencias que a forte resposta inflamatória não modulada está associada com a patogênese da LC e da LM. Embora os indivíduos SC apresentem uma resposta inflamatória mais fraca, ainda não é bem conhecido como eles controlam a infecção. Uma resposta Th1 eficiente e modulada pode estar envolvida na proteção da infecção por L. braziliensis. A modulação da resposta imune é feita principalmente por citocinas moduladoras como IL-10, TGF-β e mais recentemente por IL-27. Objetivo: Avaliar o papel de citocinas regulatórias e de antagonistas de citocinas na modulação da resposta imune na infecção por L. braziliensis. Metodologia: Células mononucleares de sangue periférico (CMSP) de 40 pacientes com LC, 18 com LM e 13 indivíduos com infecção subclínica foram estimuladas com antígeno solúvel de Leishmania (SLA) na presença e ausência de citocinas regulatórias (IL-10, IL-27 e TGF-β) ou antagonistas de citocinas (α-TNF-α e α-IFN-γ). A produção de citocinas (IL-10, IL-17, TNF-α e IFN-γ) foi mensurada através da técnica de ELISA e de Reação em Cadeia da Polimerase (PCR). Resultados: IL-10 e TGF-β apresentaram atividade moduladora da produção de TNF-α e IL-17, sobretudo na LC, enquanto IL-27 não apresentou efeito modulador na produção de TNF-α, IFN-γ e IL-17 em nenhuma das formas clínicas da leishmaniose tegumentar. A neutralização de TNF-α diminuiu a produção de IFN-γ, mas não alterou a produção de IL-10, enquanto a neutralização de IFN-γ diminuiu a produção de TNF-α e aumentou a produção de IL-10 nesses pacientes. A produção de IL-17 foi maior nos indivíduos SC, embora sem significância estatística e a neutralização de IL-10 não alterou a produção de IFN-γ nesses indivíduos. Entretanto a expressão de IL-27 foi maior em pacientes com LC quando comparado com os indivíduos SC. Conclusões: IL-10 e TGF-β parecem ser as citocinas mais envolvidas na modulação da resposta imune em pacientes com LC e LM, principalmente IL-10, desde que a neutralização de IFN-γ diminui a produção de TNF-α de uma forma dependente de IL-10. A produção de IL-17 nos indivíduos SC sugere que essa citocina pode estar envolvida na proteção contra a infecção por L. braziliensis.
Salvador
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Ruiz-Gómez, Gloria, John C. Hawkins, Jenny Philipp, Georg Künze, Robert Wodtke, Reik Löser, Karim Fahmy, and M. Teresa Pisabarro. "Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics." Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2017. http://nbn-resolving.de/urn:nbn:de:bsz:14-qucosa-215877.
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Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.
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Ruiz-Gómez, Gloria, John C. Hawkins, Jenny Philipp, Georg Künze, Robert Wodtke, Reik Löser, Karim Fahmy, and M. Teresa Pisabarro. "Rational Structure-Based Rescaffolding Approach to De Novo Design of Interleukin 10 (IL-10) Receptor-1 Mimetics." Public Library of Science, 2016. https://tud.qucosa.de/id/qucosa%3A30052.
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Tackling protein interfaces with small molecules capable of modulating protein-protein interactions remains a challenge in structure-based ligand design. Particularly arduous are cases in which the epitopes involved in molecular recognition have a non-structured and discontinuous nature. Here, the basic strategy of translating continuous binding epitopes into mimetic scaffolds cannot be applied, and other innovative approaches are therefore required. We present a structure-based rational approach involving the use of a regular expression syntax inspired in the well established PROSITE to define minimal descriptors of geometric and functional constraints signifying relevant functionalities for recognition in protein interfaces of non-continuous and unstructured nature. These descriptors feed a search engine that explores the currently available three-dimensional chemical space of the Protein Data Bank (PDB) in order to identify in a straightforward manner regular architectures containing the desired functionalities, which could be used as templates to guide the rational design of small natural-like scaffolds mimicking the targeted recognition site. The application of this rescaffolding strategy to the discovery of natural scaffolds incorporating a selection of functionalities of interleukin-10 receptor-1 (IL-10R1), which are relevant for its interaction with interleukin-10 (IL-10) has resulted in the de novo design of a new class of potent IL-10 peptidomimetic ligands.
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Konarski, Yulia. "SHP-1/ Src Complex is a Master Regulator of the IL-12/IL-23 pro- and IL-10/IL-27 Anti-inflammatory Axis in TLR4-activated Signaling Pathways in Human Monocytes and Macrophages." Thèse, Université d'Ottawa / University of Ottawa, 2013. http://hdl.handle.net/10393/25999.
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Although the etiology surrounding many autoimmune diseases remains unknown, the underlying characteristic of many of these diseases is a disruption in the balance of pro- and anti- inflammatory cytokines It is well established that the dysregulation of the IL-12 family of cytokines, an increase in IL-12/IL-23 and a decrease in IL-27 production has been implicated in these conditions. We used ELISA, RT-PCR, Immunofluorescence and Western immunoblotting in conjunction with pharmalogical inhibitors and siRNA to demonstrate the role of SHP-1/Src in the regulation of IL-12, IL-23, IL-27 and IL-10 in LPS-stimulated human THP-1 cells, monocytes and MDMs. My results show for the first time that Src kinase activity relies on SHP-1 activity, and together this complex functions in TLR4-mediated MyD88 and TRIF pathways. Furthermore Src exhibits a dual role as a positive regulator for anti-inflammatory IL-10/IL-27 and as a negative regulator of pro-inflammatory IL-12/IL-23 downstream of TLR4. Moreover, the involvement of PI3K and JNK MAPK, dependent on SHP-1/Src complex, in the regulation of IL-12 family and IL-10 downstream of TLR4 was shown.
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Walter, Johanna-Julia. "Der Einfluss von IL-10 auf die allergeninduzierte IL-4- und IL-13-Freisetzung aus basophilen Granulozyten von Patienten mit Wespengiftallergie." Diss., lmu, 2009. http://nbn-resolving.de/urn:nbn:de:bvb:19-109346.
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Hata, Hiroshi. "Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell-mediated spontaneous autoimmune arthritis in mice." Kyoto University, 2005. http://hdl.handle.net/2433/145302.
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Saunders, Ana CecÃlia de Brito. "Polimorfismo e concentraÃÃo sÃrica da interleucina-10 em hansenÃase." Universidade Federal do CearÃ, 2010. http://www.teses.ufc.br/tde_busca/arquivo.php?codArquivo=5271.
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Conselho Nacional de Desenvolvimento CientÃfico e TecnolÃgicoA hansenÃase continua sendo um problema de saÃde mundial, sendo o Brasil o segundo paÃs em maior em nÃmero de casos novos. No Cearà a doenÃa à considerada endÃmica e em 2009 foram diagnosticados 1.952 casos novos, alcanÃando um coeficiente de detecÃÃo geral de 22,8/100.00 habitantes. A doenÃa à causada pelo M. leprae, manifesta-se atravÃs de sinais e sintomas dermatoneurolÃgicos e à transmitida de pessoa a pessoa atravÃs do convÃvio de indivÃduos suscetÃveis com doentes bacilÃferos sem tratamento. A interaÃÃo do M. leprae com os subtipos de cÃlulas T produz citocinas do tipo Th1 e Th2, responsÃveis pelas diferentes formas clÃnicas da doenÃa. PadrÃes de citocinas Th1 (IL-2, IFN-γ e TNF-α) foram encontrados em lesÃes de pele das formas tuberculÃides e padrÃes de citocinas Th2 (IL-4, IL-5 e IL-10) foram encontrados em lesÃes das formas virchovianas. A hansenÃase à influenciada por vÃrios fatores, sendo os genÃticos os mais estudados no momento. Os genes das citocinas aparecem como fortes candidatos capazes de influenciar a interaÃÃo patÃgeno- hospedeiro e favorecer ou nÃo o desenvolvimento da doenÃa. A IL-10 à uma citocina anti-inflamatÃria e imunomoduladora que possui regiÃes promotoras bastantes polimÃrficas, contendo regiÃes de microssatÃlites e SNPs que formam vÃrios haplÃtipos que estÃo associados a diferentes nÃveis de produÃÃo de citocina in vitro. VÃrios estudos tentam reportar associaÃÃes entre os polimorfismos de IL-10 e o risco ou proteÃÃo para diversas doenÃas. Contudo, os dados relatados tem sido contraditÃrios e a maioria das associaÃÃes entre os polimorfismos e a produÃÃo dessa citocina sÃo baseados em estudos in vitro. Dessa forma o presente estudo teve o objetivo de definir como os polimorfismos da regiÃo promotora da citocina afetam a produÃÃo in vivo frente à infecÃÃo pelo M. leprae. Foram quantificadas as concentraÃÃes sÃricas de IL-10 de 181 indivÃduos, sendo 77 casos Ãndices de hansenÃase, 74 indivÃduos contactantes e 30 controles saudÃveis. Sendo que destes, 31 possuÃam anÃlise genotÃpica de IL-10 no grupo caso, 33 no grupo contactante e 29 no grupo controle. Os pacientes com anÃlise genotÃpica foram estratificados em baixo, mÃdio e alto produtor da citocina. As diferenÃas nos nÃveis da citocina foram comparadas entre os grupos dentro do espectro da hansenÃase (paucibacilar e multibacilar), dos controles externos, dos controles internos, dos genÃtipos e alelos encontrados nos grupos. Foram realizados testes de Kruskall-Wallis e Mann-Whitney para anÃlise das medianas de IL-10 em pg/mL. NÃo foi encontrada diferenÃa significante entre os grupos caso, contactante e controle (p=0,7450), entre os indivÃduos pauci e multibacilar (p=0,7898), entre os fenÃtipos de nÃvel de produÃÃo de citocina (baixo, mÃdio e alto) (p=0,4355). Foi encontrada diferenÃa significante na produÃÃo de IL-10 entre os alelos -1082A,-819C e -592C do grupo caso em relaÃÃo aos controles (p<0,05) e dos alelos -819C e -592C do grupo caso em relaÃÃo aos contactantes (p<0,05). NÃo foi encontrada diferenÃa significante entre os grupos contactante e controle (p>0,05). Em conclusÃo, os genÃtipos de IL-10, -1082G>A, -819C>T e -592G>C nÃo influenciaram a produÃÃo e/ou o desfecho da infecÃÃo pelo M. leprae. Por outro lado, os alelos -1082A,-819C e -592C determinaram menor produÃÃo de IL-10 em indivÃduos com hansenÃase.
Leprosy is a world problem of health and Brazil has the second higher rates of new cases in the world. It is considered an endemic disease at Cearà and a total of 1,952 new cases were detected, reaching a detection rate of 22.8/100,000 inhabitants. The interaction between the M. leprae and different T cells stimulates the production of a Th1 or a Th2 pattern of cytokines, which are responsible for the different clinical forms of leprosy. Th1 cytokines (IL-2, IFN-γ and TNF-α) were found in tuberculoid skin lesions while Th2 cytokines (IL-4, IL-5 and IL-10) were found in lepromatoid lesions. Leprosy is influenced by many distinct factors, among them, genetic factors are the most studied at this moment. Cytokine genes seem to influence the interaction between the pathogen and the host and contribute to the development or not of the disease. The IL-10 is an antiinflammatory and immunomodulatory cytokine which has too much polymorphic promoter regions with microsatellites and SNPs. Different haplotypes are associated to distinct levels of cytokine production in vitro. Many studies reported associations between IL-10 polymorphisms and the risk or the protection against many diseases. However, the data reported have been contradictory and most of the associations between these polymorphisms and the production of IL-10 are showed in in vitro studies. The aim of this study was to evaluate how the promoter region polymorphisms of IL-10 influence the cytokine levels production in vivo, during the M. leprae infection. Serum levels of IL-10 were analyzed by ELISA in 181 individuals, 77 of them were leprosy cases, 74 household contacts and 30 healthy controls. Among them, 31 had IL-10 polymorphism typed in the case group, 33 in household contact group and 29 in healthy controls. Cases with polymorphism typed were stratified in low, medium and high levels of cytokine production. Differences in the IL-10 production were compared among leprosy cases (pauci and multibacillary), household contacts, healthy controls, genotypes and alleles distribution found in the groups. Kruskall-Wallis and Mann-Whitney tests were used to analyze mean values of IL-10 levels. No differences were observed between cases, contacts and controls (p=0.7450), pauci and multibacillary (p=0.7898), phenotypes of IL-10 production (low, medium or high) (p=0.4355). A significant difference in the IL-10 levels between cases and controls was found associated to the alleles -1082A,-819C and -592C (p<0.05) and between cases and contacts associated to the alleles -819C and -592C (p<0.05). No differences were found between contacts and controls (p>0.05). In conclusion, the -1082G>A, -819C>T and -592G>C IL-10 genotypes did not influence the IL-10 production or the M. leprae infection outcome. On the other hand, -1082A,-819C e -592C alleles determined a lower production of IL-10 in cases of leprosy. Keywords: Leprosy; Polymorphisms; IL-10; Serum levels; Contacts
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Нікітіна, О. Є., Н. М. Настрадіна, Н. В. Муріна, and І. М. Стасій. "Стан продукції інтерферону-γ та інтерлейкінів IL-4 І IL-10 у хворих папіломавірусною інфекцією шийки матки." Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32270.
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Імунна відповідь організму на вірус папіломи людини (ВПЛ) включає цілий ряд факторів захисту організму від патогенної дії ВПЛ. Це - синтез імуноглобулінів, комплементу, лізоциму, активність імунних клітин, розташованих в слизовій оболонці та регіонарних лімфатичних вузлах, продукція епітеліальними клітинами імунорегуляторних цитокінів, в тому числі й інтерферонів.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32270
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Azab, Belal. "Approaches for Enhancing Therapeutic Efficacy of a Novel IL-10 Gene Family Member: MDA-7/IL-24." VCU Scholars Compass, 2011. http://scholarscompass.vcu.edu/etd/266.
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Melanoma differentiation associated gene-7 (mda-7) was discovered in the Fisher laboratory by subtraction hybridization of temporally spaced subtracted cDNA libraries prepared from terminally differentiated human melanoma cells treated with human fibroblast interferon (IFN-β) and the protein kinase C activator mezerein (MEZ), an approach called ‘differentiation induction subtraction hybridization’ (DISH). mda-7 is located in human chromosome 1q32–33 and based on sequence homology, chromosomal localization, and its functional properties, the mda-7 gene is now classified as a member of the IL-10 family of cytokines and named IL-24. The mda-7/IL-24 cDNA encodes a protein of 206-amino acids with a predicted size of ~24-kDa, which contains an interleukin (IL)-10 signature motif at amino acids 101–121 (SDAESCYLVHTLLEFYLKTVF) shared by other members of the IL-10 family of cytokines. Sequence analysis revealed the presence of a 49-amino acid signal peptide suggesting that the molecule could be cleaved and secreted. Expression of MDA-7/IL-24 protein was detected in cells of the immune system (mainly by expression in tissues associated with the immune system, such as spleen, thymus and PBMC) and normal human melanocytes. Of interest, a progressive loss of MDA-7/IL-24 expression during melanoma progression suggests an inverse relationship between MDA-7/IL-24 expression and the evolution of melanocytes to various stages of melanoma. mda-7/IL-24 induces growth suppression in human melanoma and other cancer cells, without affecting normal cells. Subsequent studies provided consistent evidence that ectopic expression of mda-7/IL-24 employing a replication incompetent adenovirus (Ad.mda-7) resulted in apoptosis induction and cell death in a wide variety of solid tumors including melanoma, malignant glioma, carcinomas of the breast, kidney, cervix, colorectum , liver, lung, ovary and prostate sparing normal cellular counterparts, i.e., such as normal melanocytes, astrocytes, fibroblasts, and mesothelial and epithelial cells. The in vitro antitumor activity of mda-7/IL-24 readily translated into the in vivo situation in animal models containing human breast, prostate, lung and colorectal carcinomas and in malignant glioma xenografts. Moreover, the ability of mda-7/IL-24 to induce a potent “bystander cancer-specific killing effect” provides an unprecedented opportunity to use this molecule to target for destruction not only primary tumors, but also metastases. Based on its profound cancer-selective tropism, substantiated by in vivo human xenograft studies in nude mice, mda-7/IL-24 (administered as Ad.mda-7) was evaluated in a Phase I clinical trial in patients with melanomas and solid cancers. These studies document that mda-7/IL-24 is well tolerated and demonstrates evidence of significant (44%) clinical activity. This review focuses on the recent enhancements in our understanding of the mode of action of mda-7/IL-24 and its potential applications as a unique and promising effective cytokine-based gene therapy for human cancers. The first chapter explored the efficacy of a tropism-modified Ad-based cancer gene therapy approach for eradicating low CAR colorectal cancer cells. We show that in low CAR human colorectal cancer cells (RKO), a recombinant Ad.5/3 virus delivering mda-7/IL-24 (Ad.5/3-mda-7) is more efficient than Ad.5 delivering mda-7 (Ad.5-mda-7) in expressing MDA-7/IL-24 protein, inducing cancer-specific apoptosis and inhibiting in vivo tumor growth in a nude mouse xenograft model. Additionally, our in vitro and in vivo data confirms that BI-97C1 (Sabutoclax) profoundly sensitizes mda-7/IL-24 mediated toxicity in colorectal cancer. Thus, Ad.5/3-mda-7, alone and/or in combination with BI-97C1 (Sabutoclax), might represent an improved and more effective therapeutic approach for colorectal and other cancers. In view of the essential roles of anti-apoptotic Bcl-2 family proteins in tumorigenesis and chemoresistance, efforts are focused on developing small molecule inhibitors of Bcl-2 family proteins as potential therapeutics for cancer. Unfortunately, due to the unique structure of Mcl-1 as compared with Bcl-2 and Bcl-xL, currently employed inhibitors, such as ABT-737 or its clinical counterpart, ABT-263, display limited affinity for Mcl-1. Using nuclear magnetic resonance (NMR) binding assays and computational docking studies, we have recently identified a series of new Apogossypol derivatives, compound 3 (BI-79D10) and compound 11 (BI-97C1), with pan-Bcl-2- inhibitory potency. BI-79D10 binds to Bcl- xL, Bcl-2, and Mcl-1 with IC50 values of 190, 360, and 520 nmol/L, respectively. BI-97C1 (Sabutoclax) is an optically pure individual Apogossypol derivative that retains all the properties of BI-79D10 along with superior in vitro and in vivo efficacy. Because Mcl-1 is over-expressed in the majority of PCs, we hypothesized that suppressing Mcl-1 by treating human PC cells with BI-97C1 (Sabutoclax) would sensitize them to mda-7/IL-24-mediated cytotoxicity. The second chapter study highlights the noteworthy potential of a combinatorial approach involving mda-7/IL-24, a broad-acting anticancer gene, and BI-97C1 (Sabutoclax), which targets Mcl-1, to sensitize PC to mda-7/IL-24-mediated cytotoxicity, thereby enhancing therapeutic efficacy. Our data suggests that treatment with the combination regimen of mda-7/IL-24 and BI-97C1 (Sabutoclax) induces autophagy that facilitates apoptosis in association with up regulation of NOXA, accumulation of Bim, and activation of Bax and Bak. Treatment with mda-7/IL-24 and BI-97C1 (Sabutoclax) inhibited the growth of PC xenografts and suppressed PC development in an immunocompetent transgenic mouse model of PC. The third chapter study explored the efficacy of a tropism-modified CRCA cancer gene therapy approach for eradicating low CAR prostate cancer cells. We showed that in low CAR PC3 cells Ad.5/3-CTV is more efficient than Ad.5-CTV in delivering transgene (mda-7/IL-24), infecting tumor cells, expressing MDA-7/IL-24 protein, inducing cancer-specific apoptosis, inhibiting in vivo tumor growth and exerting an antitumor ‘bystander’ effect in a nude mouse human prostate cancer xenograft and suppressed PC development in an immunocompetent transgenic mouse model of PC model.
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Lima, Luana Nepomuceno Gondim Costa. "Estudo do polimorfismo dos genes das citocinas TNFα, IFNγ, TGFβ, IL-6, E IL-10 em hanseníase." reponame:Repositório Institucional da UFC, 2009. http://www.repositorio.ufc.br/handle/riufc/1904.
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LIMA, Luana Nepomuceno Gondim Costa. Estudo do polimorfismo do genes das citocinas TNFa, IFNy, TGFß, IL-6, E IL-10 em hanseníase . 2009. 164 f. Dissertação (Mestrado em Microbiologia Médica) - Universidade Federal do Ceará. Faculdade de Medicina, Fortaleza, 2009.Submitted by denise santos (denise.santos@ufc.br) on 2012-01-05T12:56:35Z No. of bitstreams: 1 2009_dis_lngclima.pdf: 1702836 bytes, checksum: 54a1aa9b42b5683d9013d146e3e741d1 (MD5)
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As citocinas desempenham um papel importante na resposta imune do hospedeiro contra o M. leprae. Polimorfismos de genes de citocinas têm sido implicados como um fator do hospedeiro influenciando a susceptibilidade para doenças infecciosas. O objetivo deste estudo foi verificar a relação entre a hanseníase e os polimorfismos dos genes TNFα (fator de necrose tumoral-α) -308 G→A; IFNγ (interferon-γ) +874 T→A; IL-6 (interleucina-6) -174 G→C; IL-10 -1082 A→T, -819 C→T, -592 A→C e TGFβ (fator de crescmento tumoral-β) códon 10 e códon 25. O estudo foi realizado com moradores do município de Sobral com 15 anos ou mais, no Estado do Ceará, durante o período de março de 2006 a julho de 2008. Os indivíduos foram divididos em três grupos. O grupo caso índice foi composto por 46 indivíduos com hanseníase. Controles internos foram 110 contactantes que residiam no domicílio do caso índice e os controles externos foram 83 indivíduos que não residiam no mesmo domicílio do caso índice. Desses indivíduos foram coletados 3ml para extração de DNA através do “Genomic Prep Blood DNA Isolation Kit” (GE Healthcare) e para tipificação dos polimorfismos dos genes das citocinas através do “kit” da “One-Lambda” (Canoga Park, CA, EUA). Também forma coletados 4,9ml de sangue para detecção de anticorpos IgM para PGL-I utilizando um teste ELISA. Os dados epidemiológicos e clínicos foram obtidos a partir de um questionário aplicado à todos participantes, padronizado para o projeto “Epidemiologia da hanseníase no Ceará: aprofundamento dos estudos imuno-epidemiológicos”, ao qual esse estudo está vinculado. Assim, não foram observadas associações significantes entre os polimorfismos dos genes das citocinas estudados e a susceptibilidade à hanseníase. Em relação ao gene IL-10, os indivíduos com o genótipo GCC/GCC apresentaram uma tendência a desenvolver a hanseníase mais precocemente. Em relação aos SNPs do gene IFNγ e TGFβ encontramos uma associação do genótipo T/T do IFNγ e do genótipo T/T G/G do TGFβ com uma predisposição à doença em indivíduos vacinados, podendo ser que indivíduos com esses genótipo não sejam beneficiados com a vacina. Em relação aos SNPs do gene IL-6 do grupo de controles internos foi observada uma associação entre um considerável aumento do genótipo C/C e a positividade para o anti-PGL-I. Dessa forma, o estudo do polimorfismo dos genes das citocinas traz um melhor esclarecimento da relação entre a genética do hospedeiro e a hanseníase, complementando estudos sobre a sua transmissão e fatores intra e extra-familiares em suas características imunológicas.
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Pilon, Riccardo <1989>. "Il performance management nella pubblica amministrazione: percorsi di innovazione e il caso U.L.S.S. n. 10 "Veneto Orientale"." Master's Degree Thesis, Università Ca' Foscari Venezia, 2015. http://hdl.handle.net/10579/6757.
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La valutazione della performance, in particolare quella legata alle persone, è diventata nel corso del tempo un elemento strategico di primo piano nella gestione delle aziende. Le informazioni estrapolate dal processo di valutazione possono portare a decisioni fondamentali non solo per lo sviluppo organizzativo, ma soprattutto per individuare i punti di forza e di debolezza delle risorse umane. Nel contesto pubblico la performance ha assunto negli anni recenti un’importanza ancora più elevata, grazie alle nuove correnti di public management che impongono una forte riorganizzazione della spesa pubblica e una maggiore efficacia. In Italia questo concetto si afferma con il decreto legislativo 150 del 2009, che introduce una serie di elementi innovativi il cui scopo è stato anche quello di evitare i fallimenti passati e l’immobilismo che ha caratterizzato per lungo tempo la pubblica amministrazione. Dopo un’analisi del concetto di performance e delle implicazioni della riforma, tratteremo un caso specifico di valutazione del personale nell’ ambito sanitario, ovvero l’azienda U.L.S.S. n. 10, con lo scopo di comprendere ile implicazioni pratiche di questi nuovi principi.
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Oei, Ju Lee Women's & Children's Health Faculty of Medicine UNSW. "Inflammatory imbalance in the development of bronchopulmonary dysplasia." Awarded by:University of New South Wales. Women's and Children's Health, 2007. http://handle.unsw.edu.au/1959.4/32504.
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Abstract Introduction: Current evidence suggests that the lungs of infants with the debilitating disorder, bronchopulmonary dysplasia (BPD), react to the challenges of extra-uterine adaptation with inappropriately aggressive inflammation. The reasons for this are not entirely clear and this study hypothesizes that a deficiency of interleukin (IL)-10, a potent anti-inflammatory mediator, leads to the functional and architectural changes characteristic of BPD. Aim: To characterize the behaviour of IL-10 and neutrophil apoptosis in the tracheal fluids (TF) of infants at risk of developing BPD. Method: TF from intubated infants of varying gestations at the Royal Hospital for Women, Randwick was spun and ILs 8, 10 and 16 were measured in the supernatant. The residual pellets of white cells were used to determine differential white cell counts and neutrophil apoptosis. Results: None of the 20 TF specimens from the extremely premature infants with BPD (n=11) had detectable IL-10, compared to 14/20(70%) of the specimens from preterm infants without BPD (n=20) and to 5/19 (26%) of the specimens from term infants (n=19). BPD infants also had a significantly lower number of apoptotic neutrophils during the 1st week of life. Premature infants with TF IL-10 >5pg/ml did not develop BPD. Levels of IL-8, a neutrophil chemotaxin, and white cell counts, while not differing significantly between the groups, increased considerably towards the end of the first week of life in the BPD group. IL-16, a chemotaxin for inflammatory CD4+ cells, was also detected in more BPD than non-BPD specimens (BPD: 16/46 (35%) v 1/30 (0.3%) non-BPD preterm and 2/7 (28%) term TF specimens). Conclusions: Extremely premature infants prone to BPD have decreased pulmonary anti-inflammatory activity as demonstrated by decreased IL-10 and apoptotic neutrophils in tracheal fluids. The lack of a counter-regulatory response to the inflammatory processes that are an inevitable consequence of extra-uterine adaptation may therefore place the extremely premature newborn infant at a considerable risk of developing BPD.
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Smallie, Timothy Ian. "IL-10 mediated control of TNF gene regulation in human macrophages." Thesis, Imperial College London, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.526398.
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Ryanna, Kimuli Barbara Wasonga. "Pharmacological induction of IL-10 regulatory cells in allergy and asthma." Thesis, King's College London (University of London), 2017. https://kclpure.kcl.ac.uk/portal/en/theses/pharmacological-induction-of-il10-regulatory-cells-in-allergy-and-asthma(d01c2632-e10a-4b6d-91f8-966c004b6a77).html.
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Allergic and asthmatic disease is highly prevalent in the UK, however current treatments such as steroids, although effective in many individuals, only relieve disease symptoms, and do not provide long-lasting relief. Allergen immunotherapy can provide long-term alleviation of disease symptoms however is only effective in a proportion of patients, carries significant risk of adverse side effects and needs to be given over a prolonged period of time, often several years, for maximal efficacy. Allergic disease is associated not only with a type 2 adaptive immune response, but also impairment of regulatory T cell function. Allergen immunotherapy is associated with skewing of allergen-specific Th2 responses towards an IL-10 phenotype, suggesting that plasticity of this T cell lineage occurs in vivo. Work from our lab has shown that steroids such as dexamethasone, although non-specific in action, augment IL-10 synthesis by CD4+ T cells, a response that is enhanced by vitamin D. The major focus of this thesis was to assess whether established human CD4+ Th2 cell lines could be deviated towards an IL-10+ profile by dexamethasone and 1α25-dihydroxyvitamin D3, and whether these agents might therefore represent appropriate adjuvants to boost the antigen-specific effects of immunotherapy. Combined drug treatment of established Th2 cell lines increased Foxp3+ expression although these cells were not inhibitory in an in vitro assay of suppression. In contrast Th2 cells co-cultured with dexamethasone, 1α25-dihydroxyvitamin D3 and IL-10 over a 2-week period deviated towards an IL-10+ phenotype as assessed by qPCR and flow cytometry. Analysis of TCR-Vβ receptor usage suggested this did not represent clonal outgrowth. These cells exhibited strong suppression of Th2 cells in vitro, although this was unexpectedly not reversed by addition of neutralizing antibodies to IL-10 or TGFβ to the cell culture. Analysis of several genes previously identified to be upregulated in freshly isolated CD4+ T cells cultured with dexamethasone and 1a25-dihydroxyvitamin D3 did not reveal comparable expression by Th2-deviated IL-10+ T cells. A transcriptional gene expression array was therefore performed in order to search for biomarkers of these deviated cells and clues as to suppressive mechanisms by which they inhibit Th2 cells proliferation. Genes identified to be of interest included PDCD1LG2, BTLA and several granzymes. Granzyme expression was subsequently validated by qPCR. Severe asthma is associated not only with Th2, but also Th17 cells, therefore the capacity of 1α25-dihydroxyvitamin D3 and dexamethasone to deviate Th17-associated cytokine production was also assessed. Dexamethasone failed, and indeed could enhance IL-17A synthesis in cultures of CD4+ T cells, which may contribute to severe steroid refractory asthma. 1α25-dihydroxyvitamin D3 inhibited IL-17A synthesis in a glucocorticoid-independent manner. This work demonstrates that calcitriol and dexamethasone can be used in vitro to manipulate T cell plasticity to skew effector phenotypes towards more regulatory phenotypes. This has the potential to tailor and further develop therapeutic allergen specific regimens in vivo.
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Monteiro, Gl?ria Regina de G?is. "IL-10 na patog?nese da infec??o por Leishmania infantum." Universidade Federal do Rio Grande do Norte, 2013. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13316.
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Previous issue date: 2013-05-10Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico
Leishmaniose visceral (LV) ? uma doen?a, potencialmente, fatal cujo agente etiol?gico nas Am?ricas ? a esp?cie Leishmania infantum. No Brasil, a LV era uma doen?a predominantemente rural at? os anos 80, quando epidemias passaram a ocorrer nas grandes cidades, devido ? migra??o da popula??o para periferia dos centros urbanos, especialmente, na regi?o nordeste. A infec??o por leishmania pode evoluir com um amplo espectro cl?nico que ? dependente da resposta imune desenvolvida pelo hospedeiro. Notadamente, 80% a 90% da infec??o humana ? subcl?nica ou assintom?tica, mas os fatores que determinam a evolu??o para doen?a n?o s?o completamente esclarecidos. O controle da infec??o por leishmania ? dependente da imunidade celular mediada por IFN-. Est? demonstrado que a leishmania suprime a resposta microbicida do macr?fago. Estudos pr?vios sugerem que o perfil gen?tico do hospedeiro contribui para a evolu??o cl?nica ap?s a infec??o. O objetivo deste estudo foi avaliar o papel da Interleucina 10 na patog?nese da LV e avaliar a express?o de genes envolvidos na resposta imune, frente ? infec??o por L. infantum. Foram avaliados pessoas com LV, com infec??o assintom?tica por leishmania e doadores de sangue oriundos da ?rea end?mica para LV. Os fen?tipos foram determinados por avalia??o cl?nica, determina??o de presen?a de anticorpo antileishmania (Ac) e resposta celular (DTH). A an?lise da express?o g?nica foi realizada com amostras de RNA isoladas de pessoas na fase aguda da doen?a e tr?s meses ap?s o tratamento, utilizando c?lulas mononucleadas do sangue perif?rico, ap?s estimula??o com ant?geno sol?vel de leishmania (SLA). A m?dia IL-10 s?rico nos diferentes grupos foi: LV 91,73pg/mL ? 63,62 (n=229), DTH-AC+ 20,15pg/mL ? 25,67 (n=40), DTH+AC- 11,32pg/mL ? 10 (n=72), DTH+AC+ 9,88pg/mL ? 5,59 (n=32), DTHAC- 3,01pg/mL ? 6,59 (n=145), (p<0,01). Nas pessoas assintom?ticas, com cultura de sangue positiva para leishmania e anticorpos antileishmania positiva, a m?dia de IL-10 foi 2,18pg/mL (n=60). As pessoas com LV na fase inicial do tratamento apresentaram n?veis mais elevados de IL-10, quando comparados com os demais fen?tipos (P< 0,0001). Pessoas com o fen?tipo DTH-AC+, apresentaram n?veis de IL-10 maiores que os demais grupos com infec??o assintom?tica ou potencialmente expostos a Leishmania (DTH+AC-, DTH+AC+ e DTH-AC-). A m?dia de IL-10 entre homens e mulheres com LV foi de 103,77pg/mL ? 3,89 e 64,06pg/mL ? 4,78 mostrando uma diferen?a significativa (p<0,0001). No grupo de doadores n?o houve diferen?a significativa entre o sexo masculino 1,64pg/mL ? 6,48 e feminino 0,89pg/mL ? 11,33. Contudo os n?veis de IL-10 foram significativamente superiores na LV (p<0,0001) apontando o papel relevante desta citocina na patog?nese da doen?a. Foram identificados 362 genes com express?o diferencial entre a fase sintom?tica e p?s-recupera??o. Entre os genes expressos na fase aguda foram identificados genes relacionados ao metabolismo lip?dico, APOC1 (p<0,055 fold change -1,68), ao ciclo da ur?ia ARG1 (p<0,05 fold change -2,89) e um gene envolvido no processo biossint?tico da glicina DHFR (p<0,01 fold change -2,15). Genes codificadores de prote?nas relacionadas ? infec??o aguda, como, quimiocinas CXCL5 (p 0,032 fold change 1,92), CXCL10 (p<0,051 fold change 2,63), CCL22 (p 0,046 fold change 2,00) foram super expressos ap?s a recupera??o (tr?s meses ap?s tratamento). A compara??o da express?o g?nica evidenciou, entre outros dados, supress?o de genes de quimiocinas (CXCL5 e CXCL10), indu??o dos genes da bioss?ntese de lip?deos (APOC1) e da Arginase1. Os dados indicam vias, at? ent?o n?o relatadas, possivelmente envolvidas na patog?nese da infec??o por Leishmania infantum. A an?lise de microchips de DNA ? uma importante ferramenta para estudar a express?o g?nica global; ao mesmo tempo a IL-10 ? um marcador de doen?as e sua inibi??o ou via relacionada pode ser um potencial alvo terap?utico
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Bigot, Jérémy. "Caractérisation fonctionnelle et phénotypique de lymphocytes B transitionnels CD24hi CD38hi associés à un phénotype régulateur chez des patients transplantés rénaux traités par Belatacept." Thesis, Paris Est, 2016. http://www.theses.fr/2016PESC0071/document.
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A l’instar des lymphocytes T régulateurs, l’étude de populations lymphocytaires B au potentiel immunosuppresseur a émergé ces dernières années. La capacité immunosuppressive des lymphocytes B régulateurs CD24hi CD38hi passant notamment par leur capacité à exprimer l’IL-10 a été mise en évidence dans plusieurs pathologies notamment chez les patients atteints de maladies auto-immunes. En transplantation rénale, le rôle de ces cellules dans la tolérance du greffon a également été suggéré. Néanmoins, la caractérisation de ces cellules semble très controversée et complexe. En effet à ce jour, il n’a été mis en évidence aucun marqueur spécifique permettant d’identifier clairement cette population régulatrice chez l’homme. L’analyse transcriptomique de ces cellules issues de donneurs sains nous a permis de mettre en évidence de nouveaux marqueurs qui leur sont associés tels que CD9, CD10, CD5, ICOS-L (inducible T cell co-stimulator ligand), GARP (glycoprotein-A repetitions predominant protein) et CD1b. Nous avons pu montrer que la présence de ces marqueurs était corrélée à l’expression d’IL-10 et que l’expression de CD1b sur les cellules CD24hi CD38hi était associée à une augmentation de la capacité suppressive de ces cellules. La présence de ces cellules CD1b+ a également été retrouvée en plus forte proportion chez les patients traités par belatacept identifiés comme présentant un meilleur pronostic clinique du greffon. Des résultats préliminaires suggèrent également que d’autres mécanismes peuvent être impliqués dans la fonction immunorégulatrice des LB CD24hi CD38hi comme la sécrétion de cytokines régulatrices telles que l’IL-35. L’identification de ces molécules permet d’améliorer la caractérisation et la compréhension des mécanismes immunorégulateurs de ces cellules et pourrait être d’une grande aide pour le monitoring immunologique de la réponse humorale en transplantationLike for regulatory T cells, many studies on B cells immunoregulatory functions have emerged in the past few years. The immunosuppressive capacity of CD24hiCD38hi regulatory B cells known for their ability to produce IL-10 has been demonstrated in several pathologies, in particular in autoimmune diseases. In kidney transplant, the role of these cells in graft tolerance has also been suggested. So far, accurate phenotypic and functional analyses of these Breg are still lacking. Transcriptomic miccroarray analysis of CD24hiCD38hi B cells from healthy donors led us to identify new phenotypic markers as CD9, CD10, CD5, ICOS-L (inducible T cell co-stimulator ligand), GARP (glycoprotein-A repetitions predominant protein) and CD1b. We showed a link between this markers and IL-10 expression and we demonstrated that a CD1b marker on CD24hiCD38hi B cells was associated with an increase of regulatory properties. Breg CD24hiCD38hiCD1b+ was also found in higher frequencies in kidney transplant recipients treated with belatacept. Finally, preliminary results also suggest that other regulatory mechanisms may be involved in immunoregulatory function of CD24hiCD38hi B cells, especially through immunoregulatory cytokines such as IL-35. The identification of these molecules can improve characterization and understanding of immune-regulatory mechanisms of these cells and could be helpful in humoral response immuno-monitoring in transplantation
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Rivas, Mayorga Catalina Andrea. "Niveles de IL-6, IL-10, IL-17, IL21 y TGF-B1 asociados a la periodontitis crónica :Financiado por proyecto FONDECYT 1090046." Tesis, Universidad de Chile, 2011. http://repositorio.uchile.cl/handle/2250/133346.
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Trabajo de Investigación Requisito para optar al Título de Cirujano DentistaAutor no autoriza el acceso a texto completo de su documento
INTRODUCCIÓN: La periodontitis crónica es una enfermedad de origen infeccioso caracterizada por la interacción entre bacterias patógenas y mecanismos de defensa del hospedero. Se ha demostrado que las citoquinas IL-6, IL-21, y TGF-β participan en la diferenciación de células Th17, mientras que TGF-β , en ausencia de las otras mencionadas, induce la diferenciación de células Treg. Esto indica una fuerte relación entre células Th17 y Treg: si se favorece la producción de las primeras se fomenta la destrucción tisular, mientras que las Treg, se asocian a una respuesta protectora para los tejidos. El objetivo de este trabajo fue identificar a IL-21 y cuantificar los niveles de IL-21, IL-17, IL-6, IL-10 y TGF-β en fluido gingival crevicular (FGC) de sujetos con periodontitis crónica e individuos periodontalmente sanos. METODOLOGÍA: Se seleccionaron 20 sujetos sin periodontitis y 20 con diagnóstico de periodontitis crónica según criterios de inclusión y exclusión. Se obtuvieron muestras de FGC usando tiras de papel en sacos ≥ 5mm en enfermos, y en sitios sin signos clínicos de inflamación ni destrucción periodontal en el grupo control. La presencia de las citoquinas se determinó mediante Western-blot, y la cuantificación se realizó mediante test de ELISA. Los valores obtenidos fueron analizados con los test estadísticos correspondientes (Shapiro-Wilk y MannWhitney), considerando un p<0,05 como estadísticamente significativo. RESULTADOS: Al realizar el Western-blot fue posible identificar todos los mediadores inflamatorios mencionados. Los niveles detectados de IL-6 (1,27(1,70) pg/mL v/s 7,66(7,66) pg/mL), IL-21 (16,16(13,75) pg/mL v/s 11,38(3,21) pg/mL) e IL-10 (48,0(55,33) pg/mL v/s 4,67(7,33) pg/mL) fueron mayores en muestras de sujetos con periodontitis crónica, con una diferencia estadísticamente significativa respecto a los sanos. IL-17 (156,52(164,35) pg/mL) y TGF-β (6,92(9,63) pg/mL) fueron medibles en FGC de enfermos, pero indetectables en el de sujetos sanos. CONCLUSIÓN: Los resultados obtenidos indican que existe un desbalance entre las citoquinas relacionadas con Treg y Th17 en el FGC de individuos enfermos, con respecto a sujetos periodontalmente sanos. Esto podría ser un indicio del posible desequilibrio de estas células en periodontitis crónica, con una t endencia a la diferenciación de Th17 y, por ende, a la inflamación y destrucción tisular característica de esta patología.
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Howes, A. F. "The regulation of interleukin-10 and interleukin-12 in macrophages : investigating the differential regulation of IL-10 and IL-12 in C57BL/6 and BALB/c mice." Thesis, University College London (University of London), 2013. http://discovery.ucl.ac.uk/1409974/.
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Pattern recognition receptors (PRR) detect microbial products and induce cytokines which shape the immunological response. Interleukin-12 (IL-12) is a proinflammatory cytokine important for the differentiation of T helper 1 (Th1) cells which produce IFN-γ to activate macrophages and eradicate intracellular pathogens. In contrast, interleukin-10 (IL-10) is an immunosuppressive cytokine that minimises immune-driven host pathology, but can also lead to defective pathogen clearance. The regulation of IL-10 and IL-12 is therefore of interest due to their central roles in the orchestration of an effective but regulated immune response. C57BL/6 and BALB/c mice differ significantly in their resistance to several pathogens. We observed that macrophages generated from these mice produce reciprocal levels of IL-10 and IL-12 in response to the bacterial ligands LPS and Pam3CSK4, which activate TLR4 and TLR2 respectively, and heat-killed Burkholderia pseudomallei, a Gram-negative bacterium which activates TLR2 and TLR4. We have investigated this differential cytokine production in order to further dissect the molecular mechanisms underlying the regulation of IL-10 and IL-12. Detailed analyses of protein production, signal transduction and transcriptional kinetics have identified a type I IFN dependent, but IL-27 independent mechanism for the differential production of IL-10 in LPS and heat-killed B.pseudomallei stimulated C57BL/6 and BALB/c macrophages. Microarray analysis of LPS stimulated C57BL/6 and BALB/c macrophages further revealed potential regulatory networks that may differ between these mouse strains. These findings highlight key pathways responsible for the regulation of IL-10 and IL-12, and may provide valuable information on factors contributing to the ability of C57BL/6 and BALB/c mice to clear bacterial infections.
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Nicioli, Cristiane. "Efeito do treinamento de musculação em circuito sobre a aptidão cardiorrespiratória e citocinas plasmáticas IL-6, IL-8, IL-10, TNF, IL-1β e IL-12p70 em mulheres saudáveis." Universidade Federal de São Carlos, 2008. https://repositorio.ufscar.br/handle/ufscar/1293.
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Previous issue date: 2008-03-28Universidade Federal de Sao Carlos
There are evidences demonstrating that long-term aerobic exercises boost the plasmatic cytokines concentrations. However, there are few researches that deal with that relation in short-term and high intensity ones. This study aims at verifying the effects of strength training in circuit over the cardiorespiratory competence response and also over the plasmatic cytokines IL-6, IL-8, IL-10, IL-1β, IL-12p70 and TNF, by acute application of both tests, incremental and 35 minutes with Ventilatory Threshold (WVT) and maximum (IVO2peak) intensities. The research included 14 women, 40,23 (3,9) mean age, 164 (6,6) cm and 57,84 (7,7) kg. They did a single cycle exercise test with two stations, 30 minutes on WVT and 5 minutes on IVO2peak, just before and after strength training in circuit. The blood samples were taken at the rest time, immediately after the first and the second exercise stations for plasma cytokines analysis: interleukin 8 (IL-8), interleukin 10 (IL-10), interleukin 6 (IL-6), interleukin 12p70 (IL-12p70), interleukin 1β (IL-1 β) and tumoral necrosis factor (TNF). The cycle incremental test was conducted to verify the peak oxygen consumption (VO2peak) and the loads corresponding to the WVT and to the exhaustion. The analysis verified there are no changes in plasmatic cytokines when comparing the pre and post strength training in circuit, however, after the acute phase of the 5 minutes station in IVO2peak, there were increasing on IL- 6 during both pre [1,81 (1,36-5,05) vs. 3,09 (1,49-8,95) pg.mL-1; P=0,038] and post-training [1,62 (1,38-3,05) vs. 2,42 (1,46-5,71) pg.mL-1; P=0,021]. There were also improvement in the volunteer load [125 (100 150) vs. 150 (100-175) W; P=0,017] at the end of the intervention period. Hence, we conclude that the expression of IL-6 in plasma is protocoldependent and that the strength training in circuit does not trigger an inflammatory state, keeping the baseline concentrations of plasma cytokines unchanged. Keywords: Strength training in circuit. Cytokines. Acute phase. Ergometric cycle.
Há evidências que demonstram que exercícios aeróbios de longa duração promovem aumentos nas concentrações séricas das citocinas, porém há poucos estudos mostrando essa relação no exercício de alta intensidade e com uma curta duração. Nesse sentido, o presente estudo teve como objetivo verificar o efeito do treinamento de musculação em circuito sobre a aptidão cardiorrespiratória e sobre as citocinas plasmáticas IL-6, IL-8, IL- 10, IL-1β, IL-12p70 e TNF, através da aplicação aguda de testes incremental e de 35 minutos com intensidades no Limiar Ventilatório (WLV) e no Consumo Pico de Oxigênio (IVO2pico). O desenvolvimento do estudo contou com 14 mulheres, com média de 40,23 (3,9) anos, 164 (6,6) cm e com 57,84 (7,7) kg, que realizaram um único teste de exercício em cicloergômetro com duas estações, 30 minutos no WLV e 5 minutos no IVO2pico, nos períodos pré e póstreinamento de musculação em circuito. As coletas de sangue foram realizadas no repouso, imediatamente após a primeira e segunda estação de exercício para análise das citocinas plasmáticas: interleucina 8 (IL-8), interleucina 10 (IL-10), interleucina 6 (IL-6), interleucina 12p70 (IL-12p70), interleucina 1β (IL-1β) e fator de necrose tumoral (TNF). O teste incremental em cicloergômetro foi realizado para verificar o pico de consumo de oxigênio (VO2pico) e as cargas correspondentes ao limiar ventilatório e à exaustão. A análise não demonstrou alteração das citocinas plasmáticas ao comparar o pré e pós-treinamento de musculação, porém após a fase aguda da estaçõe de 5 minutos no IVO2pico ocorreu aumento da IL-6 no pré [1,81 (1,36 5,05) vs 3,09 (1,49 8,95) pg.mL-1; P=0,038] e pós-treinamento [1,62 (1,38 3,05) vs 2,42 (1,46 5,71) pg.mL-1; P=0,021]. Também houve melhora na carga [125 (100 150) vs 150 (100-175)W; P=0,017] das voluntárias ao término do período de intervenção. Assim, conclui-se que a expressão de IL-6 no plasma é protocolo-dependente e que o treinamento de musculação em circuito não desencadeia um quadro inflamatório, mantendo-se inalteradas as concentrações basais das citocinas plasmáticas. Palavras-chave: Treinamento de musculação em circuito. Citocinas. Efeito agudo. Cicloergômetro.
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Mattos, Marlon Fraga. "Níveis séricos e polimorfismos genéticos das interleucinas IL-6 E IL-10 em indivíduos com síndrome de down." Faculdade de Medicina de São José do Rio Preto, 2017. http://hdl.handle.net/tede/433.
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Down syndrome (DS) is the most frequent human chromosomopathy with approximate incidence of the 1 to 850 live births, nearly 90-95% of these cases are characterized by the presence of three copies of chromosome 21 as a result of the meiotic nondisjunction. DS individuals present many clinic features, including immunological changes that result in altered inflammatory response. The immune response is modulated by pro- and anti-inflammatory cytokines whose expression could be influenced by genetic polymorphisms in the coding or promoter region within the gene. Objectives: The study aimed to evaluate the frequencies of the -174G/C, -572G/C e -597G/A polymorphisms in the interleukin (IL) 6 gene promoter region and of the -592C/A, -1082A/G e -819C/T polymorphisms in the IL-10 gene promoter region in individuals with DS, and a control group without 21 trisomy, as well as to investigate the impact of the studied genotypes in the interleukins serum levels. Material and Methods: DNA samples of 200 DS individuals and 200 controls without DS were submitted to Polymerase Chain Reaction – Restriction Fragment Length Polymorphism (PCR-RFLP) or real time PCR for evaluate to presence of the -174G>C, -572G>C, and -597G>A IL-6 and -592C>A, -1082A>G, and -819C>T IL-10 polymorphisms. The serum measurement of IL-6 and IL-10 was performed in a subgroup (54 cases and 54 controls) by ELISA essay. The genotypic distribution between groups was performed by multiple logistic regression by SNPStats, program, and the linkage disequilibrium evaluation and haplotype frequency was performed by Haploview program. The comparison of IL-6 and IL-10 serum level between the groups was performed by Mann Whitney test, the interleukins concentrations analyze in relation to genotypes was performed by Kruskal-Wallis test, using the GraphPad Prism version 6.0 software. The standard error of 5% was accept. Result: Either the frequency of IL-6 and IL-10 polymorphisms or their haplotypes did not show differences between the case and control groups. There was no association between the IL-6 and IL-10 serum levels and the IL-6 and IL-10 polymorphisms. IL-10 serum levels were increased in the case group in relation to control group. Conclusion: The frequencies of the polymorphisms and haplotypes evaluated are not different between individuals with and without DS. Genotypes show no effect on the IL-6 and IL-10 serum levels. The IL-10 serum levels are increased in DS individuals, but the IL-10 polymorphisms are not the main factors that influence in higher expression of the IL-10 in DS.
A síndrome de Down (SD) é a cromossomopatia humana mais frequente, com incidência aproximada de 1 em 850 nativivos e, em cerca de 90-95% dos casos, é atribuída à trissomia livre do cromossomo 21 resultante da não-disjunção meiótica. Os indivíduos com a síndrome apresentam várias características clínicas, incluindo alterações imunológicas que resultam em resposta inflamatória alterada. A resposta imune é modulada por citocinas pró e anti-inflamatórias cuja expressão pode ser influenciada por polimorfismos genéticos na região codificante ou promotora do gene. Objetivos: O presente estudo teve como objetivos avaliar as frequências dos polimorfismos -174G/C, -572G/C e -597G/A na região promotora do gene da interleucina (IL) 6 e dos polimorfismos -592C/A, -1082A/G e -819C/T na região promotora do gene da IL-10 em indivíduos com SD, e em um grupo controle sem a trissomia do cromossomo 21 e investigar o impacto dos genótipos estudados nos respectíveis níveis séricos das interleucinas. Materiais e Métodos: Amostras de DNA de 200 indivíduos com SD e 200 controles sem a síndrome foram submetidas à reação em cadeia da polimerase - polimorfismo no comprimento dos fragmentos de restrição (PCR-RFLP) ou PCR em tempo real para avaliação da presença dos polimorfismos IL-6 -174G/C, -572G/C e -597G/A e IL-10 -592C/A, -1082A/G e -819C/T. A dosagem sérica de IL-6 e IL-10 foi realizada em um subgrupo de indivíduos (54 casos e 54 controles) pela técnica de ELISA. A distribuição genotípica entre os grupos foi realizada por regressão logística pelo programa SNPStats, e a avaliação do desequilíbrio de ligação e frequência dos haplótipos foram realizadas pelo programa Haploview. A comparação dos níveis séricos de IL-6 e IL-10 entre os grupos foi realizada pelo teste de Mann Whitney. A análise das concentrações de interleucinas em relação aos genótipos foi realizada com o teste de Kruskal-Wallis, utilizando o software GraphPad Prism versão 6.0. O erro aceito foi de 5%. Resultado: A frequência dos polimorfismos de IL-6 e IL-10 e dos seus haplótipos não mostrou diferenças entre os grupos caso e controle. Também não houve associação entre os níveis séricos de IL-6 e IL-10 e os polimorfismos de IL-6 e IL-10. Os níveis séricos de IL-10 foram aumentados no grupo caso em relação ao grupo controle. Conclusão: As frequências dos polimorfismos e haplótipos estudados não diferem entre indivíduos com SD e sem a síndrome e os genótipos não têm efeito nos níveis séricos de IL-6 e IL-10. Os níveis de IL-10 são aumentados em indivíduos com SD, mas os polimorfismos no gene IL-10 não são os principais fatores que influenciam a expressão aumentada da IL-10 na SD.