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1
Dawson, Charlotte Helen. "STAT 6 and IL-4 signalling". Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.245716.
Testo completo
2
Nieuwenhuizen, Natalie. "Immune and allergic responses to Anisakis pegreffii, with focus on the roles of IL-4, IL-13 and the IL-4 receptor alpha". Doctoral thesis, University of Cape Town, 2007. http://hdl.handle.net/11427/3115.
Testo completoAbstract (sommario):
Includes bibliographical references (p. 117-127).The fish-parasitizing nematode Anisakis pegreffii induces gastrointestinal disease and allergy when ingested by humans, and can cause occupational allergy in seafood processing workers. The present study examines immune and allergic responses to A. pegreffii in wildtype and gene deficient mice, with special focus on interleukin(IL)-4, IL-13, and the IL-4 receptor alpha (IL-4Rα). Experimental murine models of Anisakis infection, Anisakis-induced anaphylaxis and Anisakis-induced dermatitis were established in order to gain insight into the immune responses generated against Anisakis and unravel mechanisms of allergic disease.
3
Oksuz, Samet. "Targeting IL-4 locus for epigenetic reprogramming". University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1423581203.
Testo completo
4
Govender, Melissa. "Investigating the role of IL-4/IL-13 signalling through the IL-4 receptor alpha (IL-4Rα) on keratinocytes in murine models of Leishmania major and Schistosoma mansoni". Doctoral thesis, University of Cape Town, 2017. http://hdl.handle.net/11427/24890.
Testo completoAbstract (sommario):
Keratinocytes represent the major cell type in the skin. During cutaneous leishmaniasis (CL) and schistosomiasis, the skin is important during the parasite life cycle. While Th1 immunity is required to control CL, protection during schistosomiasis requires Th2 immunity. Paradoxically, Th2 characteristic IL-4 secreted early during L. major infection in mice, can drive a Th1 response by instructing dendritic cells to produce IL-12. Additionally, keratinocytes at the site of L. major infection in C57BL/6 mice, were postulated to be the source of the IL-4. We investigated if IL-4/IL-13 signalling via the IL-4Rα on keratinocytes contributed to early immunity during CL and schistosomiasis. Keratinocyte-specific IL-4Rα deficient (KRT14creIL-4Rα-/lox) BALB/c and C57BL/6 mice were generated by gene targeting and site-specific recombination (cre/loxP) under control of the KRT14 locus. In the L. major footpad model, KRT14creIL-4Rα-/lox BALB/c mice developed increased swelling, high parasite burdens, and cytokine and antibody secretion similar to littermate controls. L. major-infected KRT14creIL-4Rα-/lox C57BL/6 mice had decreased footpad swelling, low parasite burdens, a dominant Th1 cytokine response, and low type 1 and 2 antibody titres, similar to littermate control and resistant C57BL/6. In the L major ear model, KRT14creIL-4Rα-/lox BALB/c mice developed increased swelling, high parasite burdens, Th1 and Th2 cytokines, and high antibody titres, similar to littermate controls. L. major LV39-infected KRT14creIL-4Rα-/lox BALB/c mice showed significantly decreased parasite burdens in the ear, compared to littermate controls. L. major-infected KRT14creIL-4Rα-/lox C57BL/6 mice in the ear model, had decreased swelling, low parasite burdens, a dominant Th1 immune response, and low type 1 and 2 antibody titres, similar to littermate control and C57BL/6 mice. In the Schistosoma model, survival of S. mansoni-infected KRT14creIL-4Rα-/lox BALB/c mice was similar to littermate controls during mortality studies. During acute infection, S. mansoni-infected KRT14creIL-4Rα-/lox BALB/c mice showed gut pathology, hepatosplenomegaly, cytokine production, low type 1 and high type 2 antibodies, similar to littermate controls. In comparison to littermate controls, S. mansoni-infected KRT14creIL-4Rα-/lox BALB/c mice had smaller granulomas. Collectively, our results indicate that IL-4/IL-13 signalling through the IL-4Rα on keratinocytes is not required for control during CL or acute schistosomiasis, but does contribute to efficient granuloma formation during acute schistosomiasis.
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Мозгова, Юлія Анатоліївна, Юлия Анатольевна Мозговая e Yuliia Anatoliivna Mozghova. "Динаміка вмісту IL-4 та IL-6 при хронічному тонзиліті в дітей". Thesis, Сумський державний університет, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32359.
Testo completoAbstract (sommario):
Хронічне запалення піднебінних мигдаликів є розповсюдженим захворюванням дитячого віку, що несприятливо впливає на зростаючий організм. На хронічний тонзиліт страждає більше 2-3% дітей раннього віку, 6-7% - дошкільного та 8-9% школярів.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32359
6
Pizzuti, Lucas. "Síntese de 4-(fur-2-il)- e 4-(tien-2-il)-pirimidinas a partir de β-Alcoxivinil trifluormetil cetonas". Universidade Federal de Santa Maria, 2005. http://repositorio.ufsm.br/handle/1/10401.
Testo completoAbstract (sommario):
Conselho Nacional de Desenvolvimento Científico e TecnológicoThe cyclocondensation of the 1,1,1-trifluoro-4-methoxy-4-(2-heteroaryl)-3-buten-2-ones (heteroaryl = furyl and thienyl) with urea and amidines (acetamidine, benzamidine, guanidine, 1H-pyrazole-1-carboxamidine and 2-methyl-2-thiopseudourea) for synthesis of two 4-(2-heteroaryl)-6-trifluoromethylpyrimidinones and a series of ten 4-(2-heteroaryl)-6-trifluoromethylpyrimidines is reported. The reaction of the 1,1,1-trifluoro-4-methoxy-4-(2-heteroaryl)-3-buten-2-ones with urea was carried out in the presence of boron trifluoride etherate as a catalyst, at 50°C for 20 hours. The reactions of the same substracts with amidines were carried out in the presence of a 1 M solution of sodium hydroxide at r.t.-50°C for 1 hour. Under this conditions, only aromatic pyrimidines were obtained in 48-67%.
Este trabalho relata a síntese e isolamento de duas 4-(2-heteroaril)-6-trifluormetilpirimidinonas e uma série de dez 4-(2-heteroaril)-6-trifluormetilpirimidinas (heteroaril = furil e tienil), a partir da ciclocondensação de 1,1,1-trifluor-4-metoxi-4-(2-heteroaril)-3-buten-2-onas com uréia e amidinas (acetamidina, benzamidina, guanidina, 1Hpirazolil-1-carboxamidina e 2-metil-2-tiopseudouréia). A reação de 1,1,1-trifluor-4-metoxi-4-(2-heteroaril)-3-buten-2-onas com uréia ocorreu na presença de BF3.Et2O como catalisador, à 50°C por 20 horas. As reações dos mesmos substratos com amidinas ocorreu na presença de uma solução 1 M de NaOH à t.a.-50°C por 1 hora. Nestas condições, foram obtidas somente pirimidinas aromáticas com rendimentos entre 48-67%.
7
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.
Testo completoAbstract (sommario):
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.
8
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.
Testo completoAbstract (sommario):
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)
Approved for entry into archive by Eliene Nascimento(elienegvn@hotmail.com) on 2012-05-04T12:36:24Z (GMT) No. of bitstreams: 1 2000_dis_mlvale.pdf: 664941 bytes, checksum: a8df00b6a53f2d6632ebe816657800aa (MD5)
Made available in DSpace on 2012-05-04T12:36:24Z (GMT). No. of bitstreams: 1 2000_dis_mlvale.pdf: 664941 bytes, checksum: a8df00b6a53f2d6632ebe816657800aa (MD5) Previous issue date: 2000
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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Toor, Iqbal Singh. "Investigating the role of eosinophils in cardiac remodelling following myocardial infarction". Thesis, University of Edinburgh, 2018. http://hdl.handle.net/1842/31187.
Testo completoAbstract (sommario):
Myocardial infarction (MI) occurs following acute thrombotic occlusion of a coronary artery, and triggers a robust inflammatory response. Within hours, neutrophils are recruited to the infarcted myocardium followed by the infiltration of pro-inflammatory Ly6Chi monocytes. Transition from the pro-inflammatory macrophage phenotype (M1) to an anti-inflammatory, pro-resolution phenotype (M2-like) is critical to successful infarct healing. Interventions that polarize macrophages towards an anti-inflammatory 'M2-like' phenotype improve infarct healing in the experimental MI mouse model and reduce subsequent adverse remodelling of the myocardium, but the endogenous mechanisms that regulate repair are not well understood. Furthermore, differences in the resolution of inflammation in C57BL/6 and BALB/c mice, which are two of the commonly used wild-type mouse strains in experimental MI have not been characterised. We previously found that low peripheral blood eosinophil count is associated with increased short-term risk of mortality in low-intermediate risk patients with ischaemic heart disease. This suggests that eosinophils may have a role in the successful remodelling and repair of the heart following myocardial infarction. Eosinophils express a number of immuno-modulating cytokines and lipid mediators implicated in the resolution of inflammation. Increasingly prominent is interleukin-4 (IL-4), a cytokine that has been found to maintain the anti-inflammatory M2-like phenotype in macrophages. We therefore hypothesised that IL-4Rα signalling and recruitment of eosinophils to the myocardium following infarction are key in regulating the subsequent inflammatory response and scar tissue formation during infarct repair and cardiac remodelling. Experimental MI was induced by permanent left anterior descending artery ligation in isofluorane anaesthetized 12-15 week-old male wild-type (WT) BALB/c, WT C57BL/6, IL4Rα-/-, IL-4Rαflox/-, IL-4Rαflox/-LysMCre mice and eosinophil-deficient ΔdblGATA mice. Cardiac function was characterised by high-resolution ultrasound and immune cell infiltration by flow cytometry of single cell infarct and remote zone tissue digests. Blood eosinophil count and 6-month all-cause mortality were assessed in 732 consecutive patients undergoing primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (STEMI). The rate of mortality due to cardiac rupture was significantly higher in C57BL/6 mice in comparison with BALB/c mice at Day 7 post-MI. This was associated with a higher proportion of pro-inflammatory Ly-6Chi macrophages infiltrating the infarct zone tissue of C57BL/6 mice following MI. An accompanying reduction in the number of splenic Ly-6Chi monocytes post-MI, suggestive of splenic monocyte mobilisation, was seen in C57BL/6 mice but not found in BALB/c mice. Furthermore, C57BL/6 mice had a delayed transition in macrophage polarisation towards an anti-inflammatory phenotype. Disruption of IL4Rα signalling, in mice null for the IL4Rα gene, resulted in increased F4/80+ macrophage and pro-inflammatory Ly6Chi macrophage infiltration of the infarct zone and reduced expression of the anti-inflammatory macrophage marker CD206, compared to wild-type controls. Furthermore, expression of GATA3 and ST2, both associated with the immunosuppressive function of (CD4+ Foxp3+) regulatory T cells, was reduced in infarct zone regulatory T cells from IL4Rα-/- mice. These findings were associated with defective wound healing with impaired angiogenesis, increased scar size, disarrayed infarct zone collagen deposition, accompanied by modified expression of plod2 that encodes the collagen cross-linking enzyme lysyl hydroxylase 2. Resulting in greater left ventricular dilatation and loss of cardiac function, as well as a higher 7- day mortality due to cardiac rupture in IL4Rα-/- mice. This indicates that successful infarct repair requires the engagement of IL-4Rα signalling to facilitate the accumulation of anti-inflammatory macrophages and highly immunosuppressive ST2+ regulatory T cells in the heart following MI. Resident cardiac macrophages from naïve hearts of IL-4Rαflox/-LysMCre mice failed to undergo LysMCre-mediated deletion of the IL-4Rα gene, potentially because low or absent expression of Lyz2 (encoding lysozyme M). In both ST-elevation MI (STEMI) patients and mice after acute MI, there was a decline in peripheral blood eosinophil count, with activated eosinophils being recruited to the infarct zone and paracardial adipose tissue of mice. The transcription factors GATA-1 plays a role in the differentiation of eosinophils from eosinophil progenitor cells. Deletion of GATA-1 results in loss of the eosinophil lineage and has been exploited to develop the eosinophil-deficient ΔdblGATA mouse. ΔdblGATA mice were used to address the role of eosinophils in cardiac remodelling following MI. ΔdblGATA mice had increased left ventricular dilatation and reduced ejection fraction after induction of MI, relative to wild-type mice. ΔdblGATA mice had increased scar size with disarrayed infarct zone collagen deposition, accompanied by modified expression of the genes plod2 and lox, which are associated with collagen cross-linking. The proportion of CD206+ anti-inflammatory macrophages was less in the infarct zone of ΔdblGATA mice, but was restored by adoptive transfer of eosinophils from WT mice. Furthermore, adverse cardiac remodelling in eosinophil-deficient ΔdblGATA mice was rescued by provision of IL-4 complex following MI. In conclusion, an enhanced inflammatory response following MI underlies the increased risk of cardiac rupture seen with WT C57BL/6 mice in comparison to WT BALB/c mice. WT BALB/c mice are protected from cardiac rupture, which was associated with an absence of splenic monocyte mobilisation following ischaemic injury. The resolution of inflammation was found to be dependent on IL4Rα signalling which is crucial for cardiac repair and remodelling, through modulating inflammatory cell recruitment and phenotype, as well as scar formation. Eosinophils are recruited to the heart post-MI and are essential for regulating cardiac repair and remodelling, likely through provision of IL-4. Therefore, we were able to show that IL-4Rα signalling and recruitment of eosinophils to the myocardium following infarction are both key in regulating the subsequent inflammatory response and scar tissue formation during infarct healing and cardiac remodelling.
10
Dheda, Keertan Unkha Jairam. "The expression and role of IL-4 and IL-4(delta)2 in tuberculosis with and without HIV co-infection". Thesis, University College London (University of London), 2006. http://discovery.ucl.ac.uk/1445411/.
Testo completoAbstract (sommario):
Background: Tuberculosis progresses despite potent Thl responses. A putative explanation is the presence of a subversive Th2 response. However interpretation is confounded by a novel cytokine, IL-452, a splice variant and inhibitor of IL-4. Methods: The expression of Thl cytokines (IFN-y), IL-452, Th2 cytokines (IL-4) and sCD30 was investigated in whole blood, lung lavage and mononuclear cell cultures from donors with TB, TB-HIV co-infection, and matched controls. Results: After validation of a fluorogenic real-time RT-PCR assay, the half-life of IL- 4 mRNA, but not IL-452, was found to be prolonged in TB vs controls (P<0.002). mRNAs for IL-4 and IL-452 were elevated in unstimulated cells from blood and lung lavage of patients vs controls (p<0.005). Patients with TB expressed significantly greater mRNA levels of both cytokines in T-cells (p<0.05 compared to controls where expression was predominantly in non-T cells). Radiological disease correlated with the IL-4/IFN-y ratio and sCD30 (p<0.005). Tuberculosis antigen upregulated expression of IL-4 relative to IL-462 in mononuclear cell cultures from tuberculosis patients (P<0.05). By contrast, though HIV-TB co-infected donors had increased IL-4 in blood and lung lavage, in lung the predominant form was IL-452. After chemotherapy, in tuberculosis and in HIV-TB co-infection, IL-4 mRNA levels remained unchanged whilst IL-462 increased (p<0.05). Conclusions: A Th2-like response, prominent in T cells, and driven by TB antigen, is present in TB and is modulated by treatment suggesting a role for IL-4 and its antagonist, IL-452 in the pathogenesis of TB and their ratio as a possible marker of disease activity. Furthermore, enhancement of IL-4 mRNA stability, a hitherto undescribed regulatory mechanism in human TB, may facilitate the immunopathological effect of IL-4. The specific antigens inducing the IL-4 response require identification to facilitate future vaccine development strategies. Further studies are required to determine whether IL-4 facilitates systemic HIV progression in co-infected patients.
11
Green, Lisa J. "The production of IL-2, IL-4, and TNF-gas in murine leishmaniasis". Virtual Press, 1991. http://liblink.bsu.edu/uhtbin/catkey/774758.
Testo completoAbstract (sommario):
Prophylactic administration of the immunosuppressive drug cyclosporine A protects Balb/c mice from fatal Leishmania major infections. It is believed that distinct subpopulations of CD4+ T lymphocytes and their distinctive cytokines may determine susceptibility and resistance to leishmaniasis among inbred strains of mice. CsA may enhance disease resistance in Balb/c mice by modulating these T cell subsets and/or their cytokines. We have measured lymphoid cell production of IL-2, IL-4, and TNF-a in naturally resistant C57/Bl/6, CsA-treated Balb/c, and nontreated Balb/c mice during the course of L. major infection. CsA treatment inhibited IL-2 and IL-4 production for the first week of infection. Thereafter the cytokine production of all three groups of mice did not differ greatly except in week two when the treated mice produced significantly enhanced levels of IL-4. C57B1/6 mice did produce slightly more TNF-a than either group of Balb/c mice, but as the CsAprotected and diseased Balb/c mice produced similar amounts of this cytokine, the elevation in C57B1/6 animals probably reflects a strain-related difference rather than disease resistance.Department of Biology
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Rogan, David Frances. "Studies on the regulation of the Human IL-4/IL-13 gene cluster". Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289815.
Testo completo
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Worm, Margitta. "Mechanismen der CD40/IL-4-abhängigen IgE-Regulation". Doctoral thesis, Humboldt-Universität zu Berlin, Medizinische Fakultät - Universitätsklinikum Charité, 2000. http://dx.doi.org/10.18452/13716.
Testo completoAbstract (sommario):
IgE ist das Schlüsselmolekül Typ-I allergischer Erkrankungen.. Die Produktion von IgE wird durch die Interaktion des Oberflächenmoleküls CD40 auf B-Zellen mit seinem Liganden (CD40L), dass von aktivierten T-Zellen exprimiert wird, sowie über Signale durch die Zytokine IL-4 oder IL-13 von B-Zellen produziert. Die CD40/IL-4-abhängige IgE-Produktion in vitro kann einerseits als Modell zum Verständnis der Entstehung allergischer Erkrankungen eingesetzt werden; andererseits können potenziell therapeutisch wirksame Substanzen untersucht werden. Untersuchungen zum Verständnis allergischer Erkrankungen zeigen, dass LTa nach CD40/IL-4-Stimulation von humanen B-Zellen vermehrt produziert wird und dies in autokriner Weise zu einer Steigerung der CD40/IL-4-vermittelten Proliferation und IgE-Produktion führt. Darüberhinaus wurde eine vermehrte Produktion von LTa bei allergischen Patienten nachgewiesen, so dass eine funktionelle Relevanz von LTa in der Pathogenese allergischer Erkrankungen zu vermuten ist. Die Arbeiten zu den intrazellulären Mechanismen der LTa-Induktion nach CD40/IL-4-Stimulation demonstrieren, dass sowohl der Transkriptionsfaktor NF-kB als auch verschiedene Proteinkinasen hier eine wesentliche Rolle spielen. Untersuchungen mit Hilfe des CD40/IL-4-abhängigen Systems bei humanen B-Zellen, die einen therapeutischen Einsatz zur Behandlung allergischer Erkrankungen haben könnten, zeigen, dass Retinoide aber auch Vitamin D zu einer erheblichen Hemmung der IgE-Produktion in- vitro führen.IgE plays a key role for the development of type I related allergic diseases. Production of IgE by B cells is induced by the interaction of the surface molecule CD40 with its natural ligand (CD40L), which is expressed on activated T cells and signals which are provided by the cytokines IL-4 or IL-13. This model can be used for studies either to understand the development of allergic diseases or to investigate novel therapeutic approaches. In the context of the understanding the development of allergic diseases the present work shows that LTa is produced by B cells after CD40+IL-4 stimulation and that increased production of LTa results in enhanced CD40+IL-4 mediated B cell proliferation and IgE synthesis. Furthermore an increased production of LTa was shown in allergic patients indicating the potential role of LTa in allergic diseases. Analysis of the gene regulation of LTa after CD40 stimulation revealed an important role of the transcription factor NF-kB and showed the role of different protein kinases at the intracellular level. Studies using the CD40+IL-4 system in vitro which may have a therapeutical impact revealed that vitamin A and vitamin D are potent inhibitors of IgE production in vitro. Taken together the present work shows new mechanisms of CD40+IL-4 mediated IgE synthesis and also offers new potential therapeutical approaches of allergic diseases.
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Viezzer, Nicole <1993>. "Il nuovo articolo 4 dello Statuto dei lavoratori". Master's Degree Thesis, Università Ca' Foscari Venezia, 2018. http://hdl.handle.net/10579/12585.
Testo completoAbstract (sommario):
L'elaborato presenta un discorso generale sui poteri di controllo del datore di lavoro con analisi del concetto di subordinazione e relative pronunce giurisprudenziali in materia. Prosegue presentando la disciplina previgente dell'articolo 4 con esposizione delle tematiche principali quali nozioni di strumenti di controllo ed altre apparecchiature, necessità di accordo sindacale e analisi della travagliata disciplina dei controlli difensivi. Inoltre, come parte finale al capitolo 2, vengono analizzati aspetti reali quali accessi a posta elettronica, internet, telefonate e gps. Infine nel terzo capitolo, viene esposta la nuova disciplina dell'articolo 4 in cui vengono messe in evidenza le principali differenze rispetto alla disciplina presentata nel capitolo 2 ed inoltre viene analizzata in modo relativo la disciplina della privacy espressamente richiamata in articolo; nell'espletamento del capitolo è stata posta attenzione anche al nuovo trattamento che hanno subito gli strumenti di lavoro in conseguenza alla modifica della disciplina. Ultimo aspetto analizzato è invece quello dello smart working di recente emanazione con riferimento esclusivo al controllo a distanza sui lavoratori.
15
Matthews, David John. "A study of human B cell responses induced by IL-4 and IL-13". Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265340.
Testo completo
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Hibbert, Linda Margaret. "Structure and function of IL-4 and IL-13 receptors on human B cells". Thesis, University College London (University of London), 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244615.
Testo completo
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Campbell, Harding Gemma. "Regulation of IL-4 mediated signalling in primary human bronchial fibroblasts by IL-13Rα2". Thesis, University of Southampton, 2011. https://eprints.soton.ac.uk/372927/.
Testo completoAbstract (sommario):
Fibroblasts are key effector cells involved in airway inammation and remodelling in asthma. Interleukin (IL)-4 and IL-13 are important cytokines in the asthma phenotype which act on fibroblasts and other cell types. These cytokines exhibit overlapping functions through use of a common receptor, IL-4Rα:IL-13Rα1. Another receptor, IL 13 Receptor α2 (IL-13Rα2), originally thought to be a decoy receptor for IL-13, has recently been shown to attenuate responses to IL-4 as well as IL-13, by an unknown mechanism. In this thesis, I tested the hypothesis that IL-13Rα2 is responsible for the regulation of IL-4 mediated signalling in bronchial fibroblasts and that regulation by IL-13Rα2 is altered in asthma. The expression of IL-4 and IL-13 receptors on human bronchial fibroblasts (HBFs) was highly dynamic. IL-13Rα2 expression was significantly increased in response to both IL-4 and IL-13 over 24 hours, requiring de novo protein synthesis. A significant rapid reduction in IL-4Rα expression was also observed in response to either ligand, although levels rapidly returned to normal after removal of the stimulus. Use of a neutralizing antibody showed that induction of IL 13Rα2 suppressed STAT-6 activation and the pro-inflammatory effects of IL-4 and IL-13. No difference was observed in receptor expression levels or the regulatory effects of IL-13Rα2 between healthy and asthmatic subjects. IL-13Rα2 was also up regulated by a range of Th1 stimuli including IFN and IFNβ, as well as double stranded RNA (dsRNA), with no disease-related differences. The up-regulation of IL 13Rα2 in response to dsRNA hampered attempts to knock down surface expression of IL-13Rα2 using siRNA, but revealed a potential role for IL-13Rα2 in the anti-viral response due to its ability to down-regulate responses to IL-4 and IL-13. An over expression model of IL-13Rα2 identified the potential for IL-4 to cause activation of STAT3 mediated by IL-13Rα2. In HBFs naturally expressing high levels of IL-13Rα2, addition of IL-4, but not IL-13, signifycantly increased activation of STAT3, a transcription factor associated with cell survival. Whilst IL-13Rα2 may have beneficial anti-inflammatory effects by suppressing STAT-6 mediated responses, further work is required to determine potential pro-fibrotic consequences of IL-4/IL-13Rα2 mediated STAT3 activation in HBFs. Since no difference was observed in IL-13Rα2 expression or in its anti-inflammatory efficacy in HBFs from normal or asthmatic donors, these data suggest that the atopic environment is more important than intrinsic differences in the ability of asthma-derived fibroblasts to respond to IL-4 and IL-13.
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Marillier, Reece Gerrad. "The role of IL-4 and IL-13 responsiveness during Schistosoma mansoni induced inflammation". Doctoral thesis, University of Cape Town, 2008. http://hdl.handle.net/11427/3113.
Testo completoAbstract (sommario):
Includes abstract.Includes bibliographical references (leaves 117-129).
Schistosoma mansoni egg passage through intestinal tissue into the faecal stream is a critical event for completion of the life cycle of the helminth and involves induction of a type 2 immune response, which is necessary for the host’s survival. Where as T cell-specific IL-4Rα has been shown not to be essential for survival, macrophage/neutrophil-specific IL-4 receptor α-deficient mice (LysMIcre L-4Rα-/lox ), mice lacking alternative macrophages (AAMФ), had severe intestine pathology and high endotoxin levels due to poor egg excretion and dysregulated granuloma formation. This resulted in increased mortality. To determine the role of AAMФ in granuloma we aimed to describe S.mansoni egg induced granuloma formation in the presence and absence of AAMФ using LysMcreIL-4Rα-/lox mice.
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Hoving, J. Claire. "Investigating the role of IL-4/IL-13 and their receptors in ulcerative colitis". Doctoral thesis, University of Cape Town, 2010. http://hdl.handle.net/11427/3164.
Testo completoAbstract (sommario):
Ulcerative colitis (UC) is a heterogeneous inflammatory bowel disease (IBD) associated with chronic inflammation of the gastrointestinal tract. Characterized by genetic and immunological abnormalities, UC has overly aggressive T-cell responses to commensal bacteria eventually leading to disease pathology. UC is distinguished from Crohn's disease, another form of IBD, in that it is driven by a T helper type 2 (Th2) immune response. Oxazolone-induced colitis is a mouse model resembling UC presenting with inflammation limited to the distal colon and mixed neutrophil/lymphocyte infiltration in the superficial layer of the mucosa. The Th2 cytokines interleukin (IL)-4 and IL-13 are associated with the onset of oxazolone colitis and both signal through a common IL-4 receptor-alpha chain (IL-4R +-). Neutralizing these cytokines prevents or ameliorates disease significantly, while neutralizing IL-12 exacerbates disease symptoms. As many aspects of the mechanisms involving Th2 cytokines in colitis remain undefined, the aim of this study was to investigate the role of IL-4 and IL-13 and the receptors through which they signal in oxazolone-induced colitis. Previous studies have highlighted a role for IL-4 and IL-13 in mediating oxazolone colitis. We show that while IL-13-deficient BALB/c mice were protected from disease onset, IL-4R +- deficient BALB/c mice developed exacerbated disease symptoms.
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Conde, García Eva. "Anti -IL-4, -IL-13 and -IgE vaccination for the treatment of allergic diseases". Thesis, Sorbonne université, 2020. https://accesdistant.sorbonne-universite.fr/login?url=http://theses-intra.upmc.fr/modules/resources/download/theses/2020SORUS011.pdf.
Testo completoAbstract (sommario):
Les allergies représentent un problème de santé majeur avec une prévalence en nette augmentation et pour lesquelles il n’existe pas de thérapie à longue durée. L’IL-4, l’IL-13 et l'IgE jouent un rôle clé dans les réactions allergiques. Ces cibles thérapeutiques ont été validées en clinique, grâce aux anticorps monoclonaux. Néanmoins, leur utilisation reste contraignante de par leur coût excessif et la nécessité de réinjections fréquentes. L’objectif de cette thèse a été de développer des vaccins contre l’IL-4, l’IL-13 et l’IgE, appelés kinoïdes, et d’apporter la preuve de concept de l’efficacité dans des modèles d’asthme et de choc allergique. Nous avons démontré qu’une vaccination combinée contre l’IL-4 et l’IL-13 permet de réduire les taux d’IgE, l’hyperréactivité bronchique, l’éosinophilie et la production de mucus dans un modèle murin d’asthme chronique. De plus, nous avons montré qu’une vaccination avec des kinoïdes IL-4/IL-13 humains induit des anticorps neutralisants anti-IL-4 et IL-13 humaines et et réduit les niveaux d’IgE dans des souris humanisées pour l’IL-4, l’IL-13 et IL-4Ra. Nous avons également développé un vaccin conjugué contre l’IgE humaine. Nous avons montré que ce vaccin induit une forte production d’anticorps neutralisant anti-IgE humains, dans une nouvelle souche de souris humanisée pour l’IgE et le récepteur FceRI. Une vaccination des souris humanisées IgE/FceRI avec le kinoïde IgE humain réduit fortement les taux d’IgE et protège contre un choc anaphylactique induit par les IgE. L’ensemble de ces études démontre qu’une vaccination contre l’IL-4, l’IL-13 ou l’IgE pourrait représenter une solution thérapeutique contre les maladies allergiquesAllergies represent major public health problems of increasing prevalence and for which there is still no efficient long-term therapy. IL-4 and IL-13, and IgE play key roles in allergic reactions, and therefore represent good therapeutic targets. These targets have been clinically validated with approved monoclonal antibodies (mAb). However, use of mAb is limited by high cost and the need to perform repeated injections. Therefore, there is a clear need to improve current strategies in order to reach long term effects. The objective of this thesis was to develop anti-IL-4, anti-IL-13 and anti-IgE vaccines called kinoids, and provide a proof-of-concept of their safety and efficacy. We developed conjugate vaccines against IL-4 and IL-13, and demonstrated their prophylactic and therapeutic efficacy in reducing IgE levels, airway hyperresponsiveness, eosinophilia and mucus production in a house dust mite-induced mouse model of asthma without any detectable adverse effect. The human version of the IL-4/IL-13 kinoid was also efficient at neutralizing human IL-4 and IL-13, and reducing IgE levels in mice humanized for IL-4, IL-13 and their common receptor subunit IL-4Ra. In addition, we also developed a conjugate vaccine against human IgE. We showed that this anti-IgE vaccine induces long-term production of anti-human IgE neutralizing antibodies in a novel mouse strain we characterized and which is humanized for IgE and its high-affinity receptor FceRI. Anti-human IgE vaccination reduced hIgE, and fully protected against IgE-mediated anaphylaxis. Altogether, our results showed that vaccination against IL-4, IL-13 and IgE could be a valuable strategy to target allergic disorders
21
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.
Testo completoAbstract (sommario):
Orientador: Marcelo Addas CarvalhoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-21T03:08:54Z (GMT). No. of bitstreams: 1 Vilela_JosieFadul_M.pdf: 1739915 bytes, checksum: ea1d6c47907a49ccd0e00255b01d3dee (MD5) Previous issue date: 2012
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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Nogara, Pablo Andrei. "Síntese de (5-trifluormetil-1H-pirazol-1-IL)(quinolin-4-IL)metanonas de interesse farmacológico". Universidade Federal de Santa Maria, 2016. http://repositorio.ufsm.br/handle/1/10627.
Testo completoAbstract (sommario):
Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA convergent synthesis of a series of 16 new polysubstituted (5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl)(quinolin-4-yl)methanones, starting from isatin and alky(aryl/heteroaryl) ketones, is described. The diheteroaryl methanones were achieved at yields of up to 95% by a (3 + 2) cyclocondensation reaction involving 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluorobut-3-en-2-ones (by two-step reaction) and 2-alkyl(aryl/heteroaryl)-4-carbohydrazides (by three-step reaction). Subsequently, representative dehydrated heterocyclic derivatives were obtained from the respective 5-hydroxy-2-pyrazoline moieties by classical dehydration reactions, which resulted in the corresponding (5-(trifluoromethyl)-1H-pyrazol-1-yl)(quinolin-4-yl)methanones (three examples) at yields of 69 82%. The compounds were characterized by one- and two-dimensional 1H/13C NMR, X-ray diffraction, GC-MS and elemental analysis. The subsequent cytotoxicity evaluation showed that compounds with aromatic groups at the 2-position of the quinoline and a methyl moiety at the 3-position of the pyrazole have significant cytotoxicity in human leukocytes at high concentrations (200 μM).
Uma síntese convergente de uma série de 16 novos poli-substituídos (5-hidroxi-5-(trifluorometil)-4,5-di-hidro-1H-pirazol-1-il)(quinolin-4-il)metanonas, a partir da isatina e alquil(aril/heteroaril)cetonas, é descrito. As diheteroarilmetanonas foram obtidas com rendimentos de até 95% por uma reação de ciclocondensação (3 + 2) envolvendo 4-alquil(aril/heteroaril)-4-metóxi-1,1,1-trifluorbut-3-en-2-onas (reação em dois passos) e 2-alquil(aril/heteroaril)-4-carbohidrazidas (reação em três passos). Subsequentemente, os representantes desidratados dos heterociclos foram obtidos a partir das respectivas porções de 5-hidróxi-2-pirazolina por reações de desidratação clássicas, o que resultou nas correspondentes (5-(trifluormetil)-1H-pirazol-1-il)(quinolin-4-il )metanonas (três exemplos) com rendimentos de 69-82%. Os compostos foram caracterizados por RMN de 1H e 13C uni e bidimensional, difração de raios-X, CG-EM e análise elementar. As posteriores avaliações da citotoxicidade mostraram que os compostos com grupos aromáticos na posição 2 da quinolina e o grupo metila na posição 3 do pirazol, possuem significativa citotoxicidade em leucócitos humanos em concentrações elevadas (200 μM).
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Піддубна, Анна Іванівна, Анна Ивановна Поддубная, Anna Ivanivna Piddubna, Микола Дмитрович Чемич, Николай Дмитриевич Чемич e 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.
Testo completoAbstract (sommario):
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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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.
Testo completo
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Maas, Sibylle. "Die Rolle von IL-13 und IL-4 bei der Entstehung des Asthma bronchiale im Kindesalter". [S.l. : s.n.], 2007.
Cerca il testo completo
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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.
Testo completo
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Verma, Akash. "Unraveling the IL4-IL33 Nexus in Histoplasma Capsulatum Infection". University of Cincinnati / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1406898828.
Testo completo
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Michel, Marie-Laure. "Etude d’une nouvelle sous-population de lymphocytes iNKT productrice d’IL-17". Paris 6, 2008. http://www.theses.fr/2008PA066077.
Testo completoAbstract (sommario):
Les cellules iNKT (invariant Natural Killer T) constituent une population distincte de lymphocytes T matures, dont le TCR semi-invariant reflète une sélection positive par la molécule CD1d. Les cellules iNKT activées produisent rapidement et massivement des cytokines pro-Th1 (IFN-γ) et pro-Th2 (IL-4) et influencent de nombreuses maladies. Récemment, nous avons identifié une nouvelle sous-population de cellules iNKT, de phénotype NK1. 1neg, productrice d’IL-17 (iNKT17) qui sécrète peu d’IL-4 et d’IFN-γ. Ces cellules exercent notamment un rôle dans les réponses inflammatoires pulmonaires (Michel et al. JEM 2007). De plus, nous avons découvert une nouvelle voie de différenciation thymique qui donne origine aux cellules iNKT17. En effet, à l’inverse des précurseurs thymiques des cellules iNKT productrices d’IL-4 et d’IFN-γ, les cellules iNKT17 présentent le phénotype CD44high NK1. 1neg CD4neg CD8neg et gardent l'expression du facteur de transcription RORγt (Michel et al. En préparation).
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Guiter, Chrystelle. "Étude de la voie de signalisation IL-4/IL-13 dans les lymphomes B primitifs du médiastin". Thesis, Paris Est, 2008. http://www.theses.fr/2008PEST0053.
Testo completoAbstract (sommario):
Les lymphomes B primitifs du médiastin (LBPMs) constituent une entité anatomo-clinique particulière au sein des lymphomes diffus à grandes cellules B. Les analyses du transcriptome des LBPMs ont montré une forte expression des gènes induits par l’IL-4 ou l’IL-13 et des effecteurs de cette voie de signalisation. L’objectif de ce travail a été d’étudier la voie IL-4/IL-13 dans les LBPMs. Dans une 1ere partie, nous avons montré que le facteur de signalisation et de transcription 6 (STAT6) est constitutivement phosphorylé et possède une activité de liaison à l’ADN dans les lignées dérivées de LBPM (MedB1, Karpas1106). Le STAT6 phosphorylé (-P) est présent dans les noyaux des cellules tumorales de LBPMs (73% des cas). Cette activation est due en partie à l’activité de la kinase JAK2 et aux altérations du gène régulant négativement cette voie de signalisation, SOCS1. Dans une 2eme partie, nous avons étudié le rôle de STAT6 dans la physiopathologie de ces lymphomes en inhibant son expression par un siRNA dans les lignées. Nous avons montré une diminution de la prolifération et une augmentation de la mort cellulaire, ainsi qu’une diminution du taux du mRNA Bcl-xL dans les cellules MedB1. Nous avons observé une corrélation entre l’accumulation nucléaire de STAT6-P et l’expression cytoplasmique de Bcl-xL dans les cellules tumorales. Enfin, nous avons mis récemment en évidence des mutations du domaine de liaison à l’ADN de STAT6, dans 35% des LBPMs. L’étude des mécanismes oncogéniques activés dans la voie IL-4/IL-13 devrait permettre de comprendre le dysfonctionnement cellulaire à l’origine des LBPMs et pourrait aussi donner de nouvelles cibles pour le diagnostic et la thérapiePrimary mediastinal large B-cell lymphomas (PMBCLs) are a particular anatomo-clinical entity among diffuse large B-cell lymphomas (DLBCLs). The transcriptome analyses of PMBCLs showed high expression of genes activated by IL-4 or IL-13 and effectors of this signaling pathway. The objective of this work was study the IL-4 / IL-13 signaling pathway in PMBCLs. In a 1st part, we demonstrated that signal transducer and activator of transcription 6 (STAT6) is constitutively phosphorylated and exhibits DNA binding activity in PMBCL derived cell lines (MedB1, Karpas1106). This phosphorylated STAT6 (P-) is present in nuclei of PMBCL neoplastic cells (73 % of cases). This activation is partially due to the activity of JAK2 kinase and to the alteration of a gene which regulates negatively this signalling pathway, SOCS1. In a 2nd part, we studied the STAT6 role in physiopathology of these lymphomas by inhibiting its expression with a siRNA in cell lines. We showed proliferation decrease and cell death increase, as well as diminution of Bcl-xL mRNA in MedB1 cells. We observed a correlation between P-STAT6 nuclear accumulation and Bcl-xL cytoplasmic expression in neoplastic cells. In a last part, we recently demonstrate mutations of STAT6 DNA binding domain, in 35 % of PMBCLs. The study of oncogenic mechanisms activated in IL-4/IL-13 signaling pathway could allow to understand the cellular dysfunction at the origin of the PMBCLs and could also identify new targets for the diagnostic and the therapy
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Santangelo, Samantha. "Studies on the chromatin structure of the IL-4/IL-13 gene cluster in human T lymphocytes". Thesis, King's College London (University of London), 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.289840.
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Сміян, Олександр Іванович, Александр Иванович Смиян, Oleksandr Ivanovych Smiian, Вікторія Віталіївна Слива, Виктория Витальевна Слива e Viktoriia Vitaliivna Slyva. "Стан опозиційних пулів цитокінів IL-1 та IL-4 при гострих обструктивних бронхітах у дітей раннього віку". Thesis, Вид-во СумДУ, 2011. http://essuir.sumdu.edu.ua/handle/123456789/15743.
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Нікітіна, О. Є., Н. М. Настрадіна, Н. В. Муріна e 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.
Testo completoAbstract (sommario):
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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Gcanga, Lona. "IL-4/IL-13-inducible lincRNA-MIR99AHG regulates macrophage polarization and promotes intracellular survival of Mycobacterium tuberculosis". Doctoral thesis, Faculty of Health Sciences, 2020. http://hdl.handle.net/11427/32630.
Testo completoAbstract (sommario):
Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) kills 1.6 million people worldwide every year, and there is an urgent need for targeting host-pathogen interactions as a strategy to reduce mycobacterial resistance to current antimicrobials. Non-coding RNAs are emerging as important regulators of numerous biological processes and avenues for exploitation in host-directed therapeutics. Although long non-coding RNAs (lncRNAs) are abundantly expressed in immune cells, their functional role in gene regulation and bacterial infections remains under-studied. Here, we identify an immunoregulatory, lincRNA-MIR99AHG, which is upregulated in macrophages upon IL-4/IL-13 stimulation and downregulated after Mtb infection and in active TB patients. To evaluate the functional role of lincRNA-MIR99AHG, we employed antisense GapmeR-mediated lncRNA knockdown experiments. Knockdown of lincRNA-MIR99AHG with LNA-GapmeRs significantly reduced intracellular Mtb growth in mouse and human macrophages and reduced proinflammatory cytokine production. In addition, in vivo treatment with MIR99AHG LNA-GapmeRs reduced the mycobacterial burden in the lung and spleen. In vivo LNA-GapmeR treatment experiments demonstrated a role of lincRNA-MIR99AHG as a regulator of macrophage polarization and a host-mediated response post Mtb infection. Further, lincRNA-MIR99AHG translocated to the nucleus and interacts with a high affinity to hnRNPA2/B1 following IL-4/IL-13 stimulation and Mtb infection. Together, these findings identify lincRNA-MIR99AHG as a positive regulator of inflammation to promote Mtb growth and a possible for host-directed targeting or for adjunctive therapeutics against TB.
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Guiter, Chrystelle Leroy Karen Castellano Flavia. "Étude de la voie de signalisation IL-4/IL-13 dans les lymphomes B primitifs du médiastin". S. l. : S. n, 2008. http://doxa.scd.univ-paris12.fr:8080/theses-npd/th0494715.htm.
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Silva, Adriana Fernandes. "Participação das citocinas IL-4, IL-13 e IL-33 na resposta imunológica induzida pela infecção experimental por Strongyloides venezuelensis em camundongos". Universidade Federal de Minas Gerais, 2012. http://hdl.handle.net/1843/BUOS-95GJXM.
Testo completoAbstract (sommario):
Even though the importance of Th2 response in protection against nematodes is well established, the effector mechanism controlling the parasite can be different in each species. It was demonstrated in mice infected with Strongyloides venezuelensis the importance of IL-4R/Stat 6 activation in the induction of a protective response, however the involvement of IL-4, IL-13 and IL- 33 in this mechanism has not yet been established, being the main focus of this work. For this purpose, we used mice deficient in the production of IL-4 (IL-4-/ -) primarily infected or re-infected with S. venezuelensis. After infection, IL-4-/ - and wild type mice were treated with neutralizing antibody against IL-13 or exogenous IL-33. Comparing to wildtype mice, IL-4 deficient mice showed a significant increase in parasite burden and a delay in parasite elimination without changes in the fecundity. During primary infection, the IL-4 deficiency resulted in a smaller proportion of CD4+ cells in the mesenteric lymph nodes and decreased the production of IL-10, IL-5 and IFN- at the site of the lamina propria. Furthermore, the absence of IL-4 prevented IgE production, and reduced EPO and MPO levels in the host intestine. In re-infected animals, the deficiency of IL-4 resulted in an increase in the proportion of CD4+ cells in mesenteric lymph nodes and also in the intracellular detection of IL-10 in CD4+ cells in the intestinal mucosa. Along with this, the IL-4 deficiency resulted in ablation of IgE production, in a lower production of IgG1 and in a reduced degranulation of neutrophils in the intestine. The neutralization of IL-13 did not affect S. venezuelensis parasite burden but decreased the fecundity of the parasites and resulted in a lower production of parasite-specific IgM in IL-4-/- mice and an increase in eosinophil peroxidase during the infection. IL-33 administration did not affect the worm burden and fecundity but increased the IgE production by IL-4-/- mice. The results indicate that the control of S. venezuelensis infection is dependent on mechanisms mediated by IL-4 and not by IL-13 or IL-33. Moreover, the data suggests that IL-13 participates in antifecundity mechanisms during S. venezuelensis infection.Embora seja conhecido o papel fundamental da resposta Th2 na proteção contra nematódeos, sabe-se que os mecanismos responsáveis pelo controle do parasito são diferentes para cada espécie. Em camundongos infectados por Strongyloides venezuelensis foi demonstrado a importância da sinalização via IL- 4R/Stat 6 na indução de resposta protetora, entretanto a participação das citocinas IL-4, IL-13 e IL-33 neste mecanismo ainda não foi estabelecida, sendo foco principal deste trabalho. Para esta finalidade, foram utilizados camundongos deficientes da produção de IL-4 (IL-4-/-) infectados primariamente ou re-infectados por S. venezuelensis. Após a infecção, camundongos IL-4-/- e selvagens foram tratados com anticorpo neutralizante de IL-13 ou com IL-33 exógena. Em comparação com os camundongos não deficientes, camundongos IL-4-/- apresentaram aumento significativo de carga parasitária e atraso na eliminação do parasito sem alterações nos mecanismos de fecundidade. Em infecções primárias, a deficiência da produção de IL-4 acarretou em uma menor proporção de células CD4+ no linfonodo mesentérico e em diminuição de produção de IL-10, IL-5 e IFN- na mucosa intestinal. Além disso, a ausência de IL-4 impediu a produção de IgE, e diminuiu os níveis de produção de EPO e MPO. Em animais re-infectados a deficiência da produção de IL-4 acarretou em aumento da proporção de células CD4+ no linfonodo mesentérico e também em maior detecção de IL-10 em células CD4+ e na mucosa intestinal. Junto a isso, a deficiência de produção de IL-4 acarretou na ausência de produção de IgE em menor produção de IgG1 e menor desgranulação de neutrófilos no intestino. A neutralização de IL-13 durante a infecção por S. venezuelensis não interferiu na carga parasitária mas diminuiu a fecundidade dos parasitos e acarretou em uma menor produção de IgM por camundongos IL-4-/-. e em um aumento de peroxidase de eosinófilos frente a infecção. A administração de IL-33 não interferiu na carga parasitária e na fecundidade de S. venezuelensis, entretanto aumentou a produção de IgE por camundongos IL-4-/- frente a infecção. Os resultados indicam que o controle da infecção por S. venezuelensis é mediado por mecanismos dependente de IL-4 e não dependentes de IL-13 ou IL-33, sendo que IL-13 participa de mecanismos anti-fecundidade.
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Duncan, Rachel. "Understanding the molecular basis for MMP-13 repression by IL-4". Thesis, University of Newcastle upon Tyne, 2011. http://hdl.handle.net/10443/1200.
Testo completoAbstract (sommario):
Cartilage destruction in arthritic disease is characterised by irreversible collagenolysis, resulting in loss of efficient joint function. Of the enzymes capable of hydrolysing native collagen fibrils, matrix metalloproteinase-13 (MMP-13) is the major collagenolytic MMP in osteoarthritis (OA), making this MMP an important diseasemodifying target. Addition of interleukin-1 (IL-1) and oncostatin M (OSM) to bovine nasal cartilage in explant culture results in a synergistic loss of the collagen matrix, accompanied by a dramatic increase in the expression of collagenase enzymes. Interleukin-4 (IL-4) is able to ameliorate this collagen degradation by the strong repression of IL-1+OSM-induced MMP-13 expression. The aim of this work was to determine the mechanism by which IL-4 abolishes IL-1+OSM-induced MMP-13 expression. Work examining the effect of IL-4 on the methylation status of CpG residues within the MMP-13 promoter failed to identify a role for epigenetic modification in the mechanism of action of IL-4. Subsequent cell signalling studies demonstrated Akt activation by IL- 4. Therefore, genome-wide microarray analyses of cytokine stimulated cartilage and chondrocytes was used to identify candidate Akt-interacting proteins involved in the repressive effects of IL-4 on MMP-13. Trb1 was identified as a novel gene potentially involved in the repression of MMP-13 by IL-4 via Akt. Gene silencing experiments in chondrocytes confirmed that transfection with Trb1 specific siRNA resulted in the rescue of IL-4 mediated repression of IL-1+OSM-induced MMP-13 expression, indicating an anti-inflammatory role for Trb1. Trb1 belongs to family of three tribbles proteins and additional studies to investigate the roles of other tribbles family members in MMP regulation identified Trb3 as having a potentially pro-inflammatory role in MMP regulation in chondrocytes. Silencing of Trb3 was reproducibly shown to abolish IL-1+OSM-induced MMP-13 expression. The novel data presented in this thesis indicate that tribbles proteins act as key regulators of catabolic and anabolic responses in chondrocytes. From these findings it could be hypothesised that alterations in functional levels of specific tribbles proteins may protect against aberrant MMP gene expression in chondrocytes. The identification of this potentially important regulatory mechanism of signalling pathways important in MMP-13 gene expression in chondrocytes could be translated into a tractable therapy for arthritis once the mechanism has been unravelled.
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Lima, Carlos Eduardo de Oliveira. "Níveis séricos de citocinas IL-4, IL-10, IL-12, IL-17 e TNF? e de IgG/IgE aos antígenos dentinários em pacientes submetidos a tratamento ortodôntico". Universidade Estadual de Londrina, 2013. http://www.bibliotecadigital.uel.br/document/?code=vtls000182996.
Testo completoAbstract (sommario):
Objetivo: A reabsorção radicular decorrente da movimentação dentária induzida é um processo patológico de natureza inflamatória, que pode ser observada em tratamentos ortodônticos. A melhor compreensão de mecanismos imunopatológicos envolvidos nesse processo poderá contribuir para o diagnóstico precoce da reabsorção radicular. O presente estudo teve como objetivo determinar níveis séricos de citocinas e de IgG e IgE aos antígenos dentinários em pacientes submetidos a tratamento ortodôntico. Metodologia: A partir de uma amostra de 34 pacientes, foram analisadas, radiografias periapicais dos incisivos centrais superiores obtidos antes da colocação do aparelho ortodôntico (T0), aos 6-7 meses de tratamento (T1) e aos 12-13 meses de tratamento (T2), e avaliados os níveis séricos de citocinas IL-4, IL-10, IL-12, IL-17 e TNF? e imunoglobulinas IgG e IgE específicas ao antígeno dentinário humano por ensaio imunoenzimático. O extrato dentinário humano (EDH) foi obtido a partir de terceiros molares íntegros, inclusos ou semi-impactados com indicação cirúrgica, obtendo-se inicialmente, dentina em pó que foi tratada com solução desmineralizadora. Os dados foram comparados à quantidade de perda radicular observada em radiografias periapicais dos incisivos centrais superiores obtidos nas 3 fases do tratamento, analisadas pelo método de subtração radiográfica digital e reconstrução geométrica da imagem. Resultado: Os níveis de citocinas IL-10, IL-12 e IL-17 demonstraram alterações significativas, especialmente quando avaliadas em relação à extensão das reabsorções radiculares. Os níveis de anticorpos IgG e IgE ao extrato dentinário total não apresentaram diferenças significativas, todavia os níveis de IgG contra duas principais frações de EDH diminuíram significantemente no decorrer do tratamento ortodôntico sem apresentar correlação com o grau de reabsorção radicular. Conclusão: Os níveis sistêmicos de IL-4, TNF? e IgE anti-extrato dentinário permanecem inalterados no decorrer do tratamento ortodôntico, mas ocorre modulação sistêmica de citocinas IL-10, IL-12 e IL-17 dependendo do período e extensão da reabsorção e de anticopos IgG às frações de extrato dentinário independentemente do grau de reabsorção.Objective: The root resorption resulting from induced tooth movement is a pathological process of inflammatory nature, which can be seen in orthodontic treatment. A better understanding of immunopathological mechanisms involved in this process may contribute to the early diagnosis of root resorption. The present study aimed to determine serum levels of cytokines IgG and IgE to dentine antigens in patients undergoing orthodontic treatment. Methods: From a sample of 34 patients were analyzed, periapical radiographs of the maxillary central incisors obtained before placement of orthodontic appliance (T0), at 6-7 months of treatment (T1) and at 12-13 months of treatment ( T2), and evaluated the serum levels of cytokines IL-4, IL-10, IL-12, IL-17 and TNF? and IgG and IgE antigen-specific human dentinal by enzyme immunoassay. The human dentine extract was obtained from third molars intact, enclosed or semi-impacted with surgical indication, obtaining initially dentin powder that was treated with demineralizing solution. Data were compared to the amount of root loss observed in periapical radiographs of the maxillary central incisors obtained in 3 phases of treatment, analyzed by digital subtraction radiographic image and geometric reconstruction. Results: The levels of cytokines IL-10, IL-12 and IL-17 showed significant changes, especially when assessed in relation to the extension of root resorption. The levels of IgG and IgE to extract full dentin showed no significant differences, however the levels of IgG against two major fractions dentine extract decreased significantly during orthodontic treatment no correlation with the degree of root resorption. Conclusion: The systemic levels of IL-4, TNF? and anti-IgE dentine extract remain unchanged during the orthodontic treatment, but occurs modulation of systemic IL-10, IL-12 and IL-17 depending on the length and extent of resorption and antibodies IgG fractions of the extract dentin regardless of the degree of resorption.
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Oliveira, Lanussy Porfiro de. "Atividade analgésica, anti-inflamatóriae vasorelaxante de dois derivados pirazólicos: 5-[1-(4- fluorfenil)-1H-pirazol-4-IL]-2H-tetrazola(LQFM 020) e 5- [1-(2-fluorofenil)-1H-pirazol-4-IL]-2H-tetrazola (LQFM 039)". Universidade Federal de Goiás, 2014. http://repositorio.bc.ufg.br/tede/handle/tede/4876.
Testo completoAbstract (sommario):
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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES
Inflammation is a complex process that aims to protect the body eliminating the harmful agent and to promote tissue repair is characterized by classic signs: pain, heat, redness and swelling as a result of failure to resolve the inflammatory process may occur loss of function. Control of pain and inflammation leads to the search for new drugs both analgesic and antiinflammatory drugs with good efficacy to aid in the treatment of these deseases. The aim of this study was to evaluate the pharmacological effects of two pyrazole derivatives. In acute nociception tests LQFM 020 (9, 17.5 and 35 mg/kg) and LQFM 039 (17.5, 35 and 70 mg/kg) reduced the number of writhing dose dependent manner to 53, 48 and 35; and 57, 52, 42, respectively, while the control group the number of writhes was 88. In the formalin test this antinociceptive effect was confirmed by the reduction in time reactivity to pain in both test phases, the time in the control group was 78 and 72s in the first phase and 150 and 128s in the second phase, with LQFM for 020 and 039 LQFM in the first phase was to reduce 50 and 47s and the second phase to 97 and 74s respectively. In bending the tail the groups of mice treated with LQFM 020 and LQFM 039 test were not able to increase the latency to thermal stimulus demonstrated that the analgesic effect does not involve central mechanisms. Furthermore, the results of the enzymatic activity of cyclooxygenase (COX) and phospholipase (PLA2) in vitro tests indicated no part of the mechanism of action involved in the activity of these compounds. In vascular reactivity tests LQFM 020 promoted vasorelaxant effect presenting maximum effect (Emax) of 93% in aortic preparations with endothelium and maximum effect (Emax) of 91% without endothelium . LQFM 039 also promoted vasorelaxant effect with maximum effect (Emax) of 80% when tested in preparations with endothelium and maximum effect (Emax) of 76% without endothelium, given this result, we investigated the mechanism of action of these compounds. Our results showed that LQFM 020 and LQFM 039 demonstrated the involvement of NO/cGMP pathway and suggest also the involvement of sensitive Ca2+ channels in the plasma membrane voltage.
A inflamação é um processo complexo que tem como objetivo proteger o organismo, eliminando o agente lesivo, e promover a reparação tecidual sendo caracterizada por: dor, calor, rubor, edema e como consequência da não resolução do processo inflamatório pode ocorrer a perda da função. O controle da dor e inflamação leva a busca por novos fármacos tanto analgésicos quanto anti-inflamatórios com boa eficácia para auxiliar no tratamento destas doenças. O objetivo desse trabalho foi avaliar os efeitos farmacológicos de dois derivados pirazólicos. Nos testes de nocicepção aguda, LQFM 020 (9, 17,5 e 35 mg/kg) e LQFM 039 (17,5, 35 e 70 mg/kg), reduziram o número de contorções abdominais de maneira dose dependente para 53, 48 e 35 e para 57, 52 e 42, respectivamente, enquanto que no grupo controle o número de contorções foi de 88. No teste da formalina este efeito antinociceptivo foi confirmado com a redução no tempo de reatividade à dor nas duas fases do teste, o tempo no grupo controle foi de 78 e 72s na primeira fase e de 150 e 128s na segunda fase sendo que para LQFM 020 e LQFM 039 na primeira fase a redução foi para 50 e 47s e na segunda fase para 97 e 74s respectivamente. No teste de flexão de cauda os grupos de camundongos tratados com LQFM 020 e LQFM 039 não aumentaram a latência ao estímulo térmico demonstrando que o efeito analgésico não envolve mecanismos centrais. Os resultados dos testes de atividade enzimática de cicloxigenase (COX) e fosfolipase (PLA2) in vitro sugere que a inibição destas enzimas não faz parte do mecanismo de ação envolvido na atividade desses compostos. Nos testes de reatividade vascular LQFM 020 promoveu efeito vasorrelaxante apresentando efeito máximo (Emax) de 93% em preparações de aorta com endotélio e efeito máximo (Emax) de 91% sem o endotélio. LQFM 039 também promoveu efeito vasorrelaxante com efeito máximo (Emax) de 80% quando testadas em preparações com endotélio e efeito máximo (Emax) de 76% sem o endotélio, dado este resultado, foi investigado o mecanismo de ação desses compostos. Os resultados mostraram que LQFM 020 e 039 LQFM demonstram o envolvimento da via NO / GMPc e também sugerem o envolvimento de canais de Ca2+ sensíveis à voltagem na membrana plasmática.
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Stenin, Igor [Verfasser]. "Die Freisetzung von IL-4, IL-13, IL-33, sST2 und Eotaxin 3 nach nasaler Allergenprovokation bei Probanden mit allergischer Rhinitis / Igor Stenin". Düsseldorf : Universitäts- und Landesbibliothek der Heinrich-Heine-Universität Düsseldorf, 2016. http://d-nb.info/1100688846/34.
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Vides, Juliana Peloi [UNESP]. "Expressão gênica das interleucinas IL-4, IL-10, IL-12 e de interferon gama no baço de gatos infectados por Leishmania infantum chagasi". Universidade Estadual Paulista (UNESP), 2014. http://hdl.handle.net/11449/126309.
Testo completoAbstract (sommario):
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000840958.pdf: 626379 bytes, checksum: cdcf4314b4ef6a4265388d09c2020f3f (MD5)tentativa de compreender a resposta imune de gatos com leishmaniose visceral, o presente estudo teve como objetivo avaliar a expressão gênica das interleucinas IL-4, IL-10, IL-12 e de IFN-γ por reação em cadeia da polimerase em tempo real em amostras de baço de felinos naturalmente acometidos pela doença. Para tanto foram avaliados três grupos de animais; o primeiro e o segundo grupos compostos por seis gatos infectados por Leishmania cada, sintomáticos e assintomáticos, respectivamente; e o terceiro por seis gatos clinicamente hígidos e não infectados. Nos gatos sintomáticos, as expressões de mRNA das citocinas IL-4, IL-10, IL-12 e IFN-γ estavam reduzidas em 2,52; 2,4; 2,3 e 0,57 vezes em relação ao grupo controle, respectivamente. Nos animais assintomáticos, as expressões de IL-4, IL-10, IL-12 e de IFN-γ foram, respectivamente, de 2,22; 2,15; 2,52 e 1,15 vezes menores quando comparadas ao grupo controle. Ainda, uma forte correlação foi observada entre as expressões de IL-4 e de IL-10 nos gatos sintomáticos, e entre IFN-γ e IL-10, IL-12 e IL-4 e entre IL-12 e IL-10 nos gatos assintomáticos. A redução na expressão das quatro citocinas analisadas evidencia pequena participação dos linfócitos Th1 e Th2 na resposta frente à infecção por Leishmania spp. em gatos, independente do estado clínico dos animais
TIn an attempt to understand the immune response of cats with visceral leishmaniasis, the present study aimed to evaluate the gene expression of interleukins IL- 4, IL-10, IL-12 and IFN-γ by real-time polymerase chain reaction in samples of spleen from cats naturally affected by the disease. For this, three groups of cats were evaluated; the first and second groups composed of six Leishmania-infected cats each, symptomatic and asymptomatic, respectively; and the third composed of six clinically healthy and uninfected cats. In symptomatic cats the mRNA expressions of IL- 4, IL -10, IL - 12 and IFN- γ were respectively supressed 2.52, 2.4, 2.3 and 0.57 times compared to the control group. In asymptomatic animals the expression of IL- 4, IL -10, IL -12 and IFN- γ were, respectively, 2.22, 2.15, 2.52 and 1.15 times lower when compared to the control group. Also, a strong correlation was observed between the expressions of IL4 and IL-10 in symptomatic cats; between IFN-γ and IL-10, IL-12 and IL-4 and between IL-12 and IL-10 in asymptomatic cats. The reducion of expression the four cytokines analyzed evidences a small involvement of Th1 and Th2 lymphocytes in the response to infection by Leishmania spp. in cats, regardless of the clinical status of animals
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Vides, Juliana Peloi. "Expressão gênica das interleucinas IL-4, IL-10, IL-12 e de interferon gama no baço de gatos infectados por Leishmania infantum chagasi /". Araçatuba, 2014. http://hdl.handle.net/11449/126309.
Testo completoAbstract (sommario):
Resumo: tentativa de compreender a resposta imune de gatos com leishmaniose visceral, o presente estudo teve como objetivo avaliar a expressão gênica das interleucinas IL-4, IL-10, IL-12 e de IFN-γ por reação em cadeia da polimerase em tempo real em amostras de baço de felinos naturalmente acometidos pela doença. Para tanto foram avaliados três grupos de animais; o primeiro e o segundo grupos compostos por seis gatos infectados por Leishmania cada, sintomáticos e assintomáticos, respectivamente; e o terceiro por seis gatos clinicamente hígidos e não infectados. Nos gatos sintomáticos, as expressões de mRNA das citocinas IL-4, IL-10, IL-12 e IFN-γ estavam reduzidas em 2,52; 2,4; 2,3 e 0,57 vezes em relação ao grupo controle, respectivamente. Nos animais assintomáticos, as expressões de IL-4, IL-10, IL-12 e de IFN-γ foram, respectivamente, de 2,22; 2,15; 2,52 e 1,15 vezes menores quando comparadas ao grupo controle. Ainda, uma forte correlação foi observada entre as expressões de IL-4 e de IL-10 nos gatos sintomáticos, e entre IFN-γ e IL-10, IL-12 e IL-4 e entre IL-12 e IL-10 nos gatos assintomáticos. A redução na expressão das quatro citocinas analisadas evidencia pequena participação dos linfócitos Th1 e Th2 na resposta frente à infecção por Leishmania spp. em gatos, independente do estado clínico dos animaisAbstract: TIn an attempt to understand the immune response of cats with visceral leishmaniasis, the present study aimed to evaluate the gene expression of interleukins IL- 4, IL-10, IL-12 and IFN-γ by real-time polymerase chain reaction in samples of spleen from cats naturally affected by the disease. For this, three groups of cats were evaluated; the first and second groups composed of six Leishmania-infected cats each, symptomatic and asymptomatic, respectively; and the third composed of six clinically healthy and uninfected cats. In symptomatic cats the mRNA expressions of IL- 4, IL -10, IL - 12 and IFN- γ were respectively supressed 2.52, 2.4, 2.3 and 0.57 times compared to the control group. In asymptomatic animals the expression of IL- 4, IL -10, IL -12 and IFN- γ were, respectively, 2.22, 2.15, 2.52 and 1.15 times lower when compared to the control group. Also, a strong correlation was observed between the expressions of IL4 and IL-10 in symptomatic cats; between IFN-γ and IL-10, IL-12 and IL-4 and between IL-12 and IL-10 in asymptomatic cats. The reducion of expression the four cytokines analyzed evidences a small involvement of Th1 and Th2 lymphocytes in the response to infection by Leishmania spp. in cats, regardless of the clinical status of animals
Orientador: Mary Marcondes
Banca: Wagner Luis Ferreira
Banca: Maria cecília Rui Luvizotto
Banca: Márcia Dalastra Laurenti
Banca: Raimundo Souza Lopes
Doutor
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Sarkar, Sujata, Laura Cooney, Peter White, Deborah Dunlop, Judith Endres, Julie Jorns, Matthew Wasco e David Fox. "Regulation of pathogenic IL-17 responses in collagen-induced arthritis: roles of endogenous interferon-gamma and IL-4". BioMed Central, 2009. http://hdl.handle.net/10150/610381.
Testo completoAbstract (sommario):
INTRODUCTION:Interleukin (IL)-17 plays an important role in the pathogenesis of rheumatoid arthritis and the mouse model collagen-induced arthritis (CIA). Interferon(IFN)-gamma and IL-4 have been shown to suppress Th17 development in vitro, but their potential immunoregulatory roles in vivo are uncertain. The goals of this study were to determine the relationship between Th17 responses and disease severity in CIA and to assess regulation of IL-17 by endogenous IFN-gamma and IL-4.METHODS:DBA1/LacJ mice were immunized with type II collagen in complete Freund's adjuvant (CFA) to induce arthritis, and treated with neutralizing antibody to IFN-gamma and/or IL-4. Systemic IL-17, IFN-gamma, and IL-4 were measured in serum. At the peak of disease, cytokine production was measured by ELISA of supernatants from spleen, lymph node and paw cultures. Paws were also scored for histologic severity of arthritis.RESULTS:Joint inflammation was associated with a higher ratio of systemic IL-17/IFN-gamma. Neutralization of IFN-gamma accelerated the course of CIA and was associated with increased IL-17 levels in the serum and joints. The IFN-gamma/IL-4/IL-17 responses in the lymphoid organ were distinct from such responses in the joints. Neutralization of IL-4 led to increased arthritis only in the absence of IFN-gamma and was associated with increased bone and cartilage damage without an increase in the levels of IL-17.CONCLUSIONS:IL-4 and IFN-gamma both play protective roles in CIA, but through different mechanisms. Our data suggests that the absolute level of IL-17 is not the only determinant of joint inflammation. Instead, the balance of Th1, Th2 and Th17 cytokines control the immune events leading to joint inflammation.
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Лаврюкова, С. Я., Н. С. Пастерначенко, В. О. Мозгова, О. М. Усиченко e К. М. Усиченко. "Аналіз частоти виявлення деяких поліморфізмів генів цитокінів IL-4, IL-10, TNF у хворих на хронічний гепатит В". Thesis, Сумський державний університет, 2016. http://essuir.sumdu.edu.ua/handle/123456789/45438.
Testo completoAbstract (sommario):
Хронічний гепатит В (ВГВ) є однією з основних причин хронічних дифузних захворювань печінки. У хворих на ХГВ є високий ризик розвитку цирозу печінки, печінково-клітинної недостатності і гепатоцелюлярної карциноми. Дослідженнями останніх років доведено, що дисбаланс секреції імунорегуляторних цитокінів та регуляції цітокінопосредованої кооперації, проліферації і диференціювання клітин, може бути обумовлений комплексом генів, від яких залежить рівень продукції цитокінів Th1 або Th2 типу. Встановлено, що рівень продукції цитокінів та їх антагоністів, експресія рецепторів до різних цитокінів визначається успадкованим індивідуумом набором алельних варіантів генів цитокінів та їх рецепторами. Однак, дослідження з вивчення взаємозв'язку між поліморфізмом генів цитокінів та варіантами перебігу ХГВ нечисленні і нерідко оцінюються в одній групі з хронічним гепатитом С.
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Піддубна, Анна Іванівна, Анна Ивановна Поддубная e Anna Ivanivna Piddubna. "IL-4, IL-10 and TNF-α Promotor Gene Polymorphism in North-Eastern Ukrainian HIV-1 Infected Individuals". Thesis, Global HIV Vaccine Enterprise, 2013. http://essuir.sumdu.edu.ua/handle/123456789/32398.
Testo completoAbstract (sommario):
Вивчено характер розподілу алельних варіантів промотерної ділянки гену IL-4 у позиції -590, IL-10 у позиції -592, TNF-α у позиції -308 у ВІЛ-інфікованих українців Північно-Східного регіону.
При цитуванні документа, використовуйте посилання http://essuir.sumdu.edu.ua/handle/123456789/32398Изучен характер распределения аллельных вариантов промотерных участков генов IL-4 в позиции -590, IL-10 в позиции -592, TNF-α в позиции -308 у ВИЧ-инфицированных украинцев Северо-Восточного региона. При цитировании документа, используйте ссылку http://essuir.sumdu.edu.ua/handle/123456789/32398
The distribution character of the allel variants of IL-4 promoter gene area in position -590, IL-10 in position -592, TNF-α in position -308 in HIV-infected Ukrainians of North-Eastern region was studied. When you are citing the document, use the following link http://essuir.sumdu.edu.ua/handle/123456789/32398
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Squilloni, Sofia <1993>. "Bing Xin tra il 1900 e il 1920: un'analisi storico-biografica a cento anni dal 4 Maggio 1919". Master's Degree Thesis, Università Ca' Foscari Venezia, 2019. http://hdl.handle.net/10579/15102.
Testo completoAbstract (sommario):
Il presente lavoro di tesi prende in esame l’infanzia, la giovinezza e una parte della prima produzione letteraria di Bing Xin (pseudonimo di Xie Wanying), scrittrice, poetessa e traduttrice cinese vissuta tra il 1900 e il 1999. Ripercorrendo le tappe fondamentali della prima parte della sua biografia attraverso la traduzione e l’analisi di alcune memorie autobiografiche appartenenti all’età matura della scrittrice, il presente lavoro si propone di analizzare, secondo una prospettiva tematica, i primi racconti della vastissima opera di Bing Xin, collocandoli nel contesto storico in cui vennero scritti e cercando di comprendere i legami tra l’autrice e il Movimento del 4 Maggio 1919, movimento di profonda importanza e cambiamento nel panorama della cultura, della letteratura e del pensiero politico cinese. La scelta di adottare una prospettiva biografica e storica, articolata in un’analisi dei primi vent’anni di vita di Bing Xin e del quadro storico in cui si collocano, deriva dalla convinzione che l’esperienza personale dell’autrice e il contesto storico-familiare in cui è nata e cresciuta abbiano rivestito un ruolo di grande rilevanza nella scelta dei temi trattati nei suoi primi racconti, influenzando anche alcune sue posizioni “tradizionaliste”, o quantomeno caute, a livello ideologico, riguardo a determinati argomenti di rottura nei confronti della tradizione portati avanti del Movimento rivoluzionario del 4 Maggio.
Il primo capitolo si concentra sugli elementi principali che hanno caratterizzato l’infanzia di Bing Xin, proponendo la traduzione del breve testo autobiografico “Mia madre” e del racconto “Sul mare”.
Il secondo capitolo è dedicato alla prima adolescenza di Bing Xin, iniziata a partire dal suo arrivo a Pechino nel 1913. La prima parte del capitolo presenta una descrizione storica della situazione culturale, sociale ed economica in cui si trovava la capitale tra la fine del 1800 e il primo ventennio del 1900. La seconda parte si concentra sulla descrizione dei primi anni di vita della famiglia Xie a Pechino e sull’entrata della futura scrittrice nella Bridgman Academy. Viene proposta la traduzione di una parte del testo autobiografico “Il mio arrivo a Pechino” e del testo “La scuola Bridgman”.
Il terzo capitolo si concentra sul Movimento del 4 Maggio 1919, presentando le principali istanze di rinnovamento culturale portate avanti dagli intellettuali di allora e cercando di comprendere le influenze che tale movimento esercitò su Bing Xin, la quale cominciò a scrivere i suoi primi racconti proprio sull’onda del fermento culturale che attraversava la capitale in quegli anni. Viene proposta la traduzione di due tra i primi racconti scritti da Bing Xin negli anni ’20 del 1900 e di un terzo testo che segna il passaggio, nella produzione della scrittrice, da una fase iniziale di letteratura “impegnata” (quella dei wenti xiaoshuo 问题小说) ad una che si concentra maggiormente sui rapporti umani e sull’importanza che l’amore, intenso in senso ampio e generalizzato, riveste nella vita umana.
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Belo, Vanessa de Almeida. "Expressão de genes da resposta imune em bovinos infestados com carrapatos (Boophilus microplus)". Universidade Federal de Juiz de Fora (UFJF), 2008. https://repositorio.ufjf.br/jspui/handle/ufjf/2841.
Testo completoAbstract (sommario):
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Nos países tropicais, as perdas causadas pela infestação de carrapatos em bovinos acarretam um grande impacto no sistema de produção animal. Recentes estudos têm mostrado a importância de fatores genéticos ligados a resistência a carrapato em Bos taurus indicus e Bos taurus taurus e que as citocinas têm um papel crítico na prevenção ou progressão de doenças. O objetivo desse trabalho foi avaliar os níveis de expressão dos genes IL-10 e IL-4 relacionados ao perfil imunológico Th2 associado à susceptibilidade ao carrapato e os genes IL-2 e IFN- relacionados ao perfil imunológico Th1 associado à resistência ao parasito. Além destes genes, analisou-se o perfil de expressão do gene TLR-2, importante no processo de reconhecimento de patógenos e os genes IL-8 e TNF-α importantes no processo inflamatório inicial. Seis animais mais resistentes e seis animais mais susceptíveis de uma população F2 de 332 animais, originária do cruzamento de animais F1(½ Holandês: ½ Gir), foram selecionados baseado na contagem de carrapatos e valor genético. Amostras de tecido foram coletadas de pele no 5° e 12° dias após a infestação para extração de RNA total. As PCRs em tempo real foram realizadas usando o gene GAPDH como controle endógeno. Os animais resistentes e susceptíveis apresentaram aumento de expressão do gene IL-10 no 5° (p<0,01) e 12 ° dias após a infestação (p<0,05). O gene IL-2, nos animais resistentes e susceptíveis, no 5° dia após a infestação não apresentou alteração da expressão sendo que 12° dia, em ambos os grupos de animais, este gene passou a ser mais expresso em relação ao animal controle sugerindo um perfil de resposta imunológica do tipo de Th2 nos animais resistentes e susceptíveis nos primeiros dias após a infestação. O gene IL-4 apresentou uma tendência ao aumento de expressão nos animais resistentes e susceptíveis em relação ao controle, sendo o perfil Th2 sugerido atribuído a IL-10 produzida por linfócitos T regulatórios (p>0,05). O gene TNF- apresentou aumento de expressão nos animais susceptíveis no 5° dia após a infestação com posterior diminuição no 12° dia após a infestação (p<0,05). Nos animais resistentes não foi observada alteração da expressão deste gene, isto sugere que ele possa estar mais atuante no início do processo inflamatório, logo após a fixação do carrapato. A mesma observação estende-se para o gene IL-8, em que não foi verificada alteração de expressão nos animais resistentes, embora nos animais susceptíveis este gene apresentou diminuição da expressão no 12° dia após a infestação (p<0,05). Quanto ao gene IFN-, não houve diferença de expressão entre os animais resistentes e susceptíveis, sendo que este gene parece não estar relacionado ao mecanismo de resistência. O gene TLR-2 apresentou diminuição da expressão em ambos os grupos de animais. Estes resultados sugerem que a resposta imune adquirida avaliada neste trabalho não apresenta papel preponderante no mecanismo de resistência e que resposta imune inata poderia está envolvida no mecanismo de resistência ao carrapato. Portanto, avaliação da resposta imunológica horas após a fixação do carrapato poderia nos fornecer resultados mais conclusivos.
In tropical countries losses caused by tick infestation in cattle lead to a major impact on animal production systems. Recent studies have shown the importance of genetic factors linked to tick resistance in Bos indicus and Bos taurus as well as the critical role in the prevention or progression of diseases mediated by cytokines. The aim of this work was to evaluate gene expression of IL-10 and IL-4 in relation to tick susceptibility associated with the Th2 profile and gene expression of IL-2 and IFN- in relation to tick resistance associated with the Th1 profile. In addition, the expression of TLR-2, important in the process the recognition of pathogens, and TNF-α and IL-8 genes, important in the initial inflammatory process, were evaluated. Six tick-resistant and six tick-susceptible animals from a F2 population of 332 animals, originated from the cross of F1 animals (½ Holstein: ½ Gir), were selected based on tick count and breeding value for tick resistance. Skin biopsies were collected in the 5th and 12th days after tick infestation. The GAPDH was used as endogenous control to normalize the amount of starting cDNA target in the real-time PCR assay. Both resistant and susceptible animals showed increased gene expression of IL-10 in the 5th and 12th days after infestation in relation to control animal (p<0.05). The IL-2 gene showed no change of expression in the 5th day after infestation for the resistant and susceptible animals. In the 12th post infestation, both resistant and susceptible animals showed increased gene expression in relation to control animal. These results suggest an enhancement of Th2 profile through the increase of IL-10 mRNA levels and a possible inhibition of the Th1 pattern in both groups (resistant and susceptible) starting 5 days after infestation and return to normal by day 12. Despite our results suggest the occurrence of the Th2 profile, the susceptible and resistant animals did not show variation on gene expression for IL-4 in relation to control animal. The susceptible animals showed increased expression of TNF-α in the 5th day after infestation. However, in the 12th day post infestation it was noted a decrease in the gene expression level. The resistant animals showed no change in the expression of this gene in relation to control animals suggesting that TNF-α could be more actively expressed in the early steps of the inflammatory process. Similarly, the resistant animals showed no variation in the expression of IL-8 while the susceptible animals showed increased expression in the 12th day post infestation. There were no differences of expression between resistant and susceptible animals in relation to IFN-γ what suggests that this gene might not be involved in the resistance mechanism. The TLR-2 gene showed decreased expression in both resistant and susceptible animals (p<0.05). Finally, there was no difference in expression between susceptible and resistant animals in relation to all selected genes in the 5th and 12th days after infestation. These results suggest that the acquired immunity evaluated in this work might not have preponderant role in the resistance mechanism. The innate immunity might be playing a major role in the bovine tick resistance/susceptibility mechanism in early hours after infestation.
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Bombardieri, Cíntia Raquel. "O circuito p38MAPK/MSK1 influencia o período inicial de diferenciação Th1/2". Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/42/42133/tde-30012008-145520/.
Testo completoAbstract (sommario):
O sistema imune dos mamíferos forma uma complexa rede de populações celulares especializadas e vias de sinalização extremamente reguladas. Linfócitos T naïve podem diferenciar-se após encontro com o antígeno em pelo menos duas sub-populações distintas, Th1 ou Th2, sendo que o papel do circuito p38MAPK/MSK1 durante este período inicial de ativação não é completamente entendido. Linfócitos T CD4+ naïve humanos foram estimulados in vitro em condições não-polarizantes (Tnp), Th1 ou Th2, na presença de inibidor específico da p38MAPK. As células ativadas e mantidas em condições diferenciadoras Th1 ou Th2 na presença do inibidor SB203580, apresentaram menor produção de IFN-g e maior produção de IL-4. Através do bloqueio do RNAm da MSK1 por siRNA, observamos o mesmo efeito resultante da inibição da p38MAPK, fato que foi confirmado em experimentos com linfócitos T de camundongos MSK1-deficientes. A alteração da produção das citocinas características de cada população parece ser decorrente da alteração da expressão da IL12Rb2 e IL4R-a dos receptores de citocinas da IL-12 e IL-4, respectivamente. Desta forma, os nossos dados sugerem que o circuito p38MAPK/MSK1 participa do processo de ativação dos linfócitos T mantidos em condições diferenciadoras Th1/2.The mammalian immune system form a complex network of highly regulated signaling pathways and populations of specialized cells. After meeting with the antigen naïve T cells differentiate into at least two distinct sub-populations, Th1 or Th2, and the role of the circuit p38MAPK/MSK1 during this initial period of activation is not completely understood. Human CD4+ T lymphocytes were stimulated in vitro under non-polarized, Th1 or Th2 conditions, in the presence of a specific p38MAPK inhibitor. The cells activated and differentiated under Th1 or Th2 condition in the presence of inhibitor SB203580, had decreased production of IFN-g and increased IL-4. By silencing MSK1 through siRNA, we observed the same effect due to inhibition of p38MAPK, an observation that was confirmed in experiments with T lymphocytes from mice deficient of MSK1. The change in the production of cytokines appears to be a result of altered expression of IL12R-b2 and IL4Ra receptors of the cytokines IL-12 and IL-4, respectively. Taken together, our data suggest that the circuit p38MAPK/MSK1 plays a key role in the activation of human T cells maintained under Th1/2 differentiation conditions.
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Lourenço, Roseli Maria de Conti. "Sintese,toxicidade e atividade tripanocida de 3-(4'-bromo-[1,1'-bifenil]-4-il-)-3-(4-x-fenil)-N,N-dimetil-2-propeno-1-amina". [s.n.], 1996. http://repositorio.unicamp.br/jspui/handle/REPOSIP/248924.
Testo completoAbstract (sommario):
Orientador: Nelson Eduardo Duran CaballeroTese (doutorado) - Universidade Estadual de Campinas, Instituto de Quimica
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Doutorado
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Stupfel, Marine. "Reconnaissance de surfaces de protéines par des foldamères aromatiques". Thesis, Bordeaux 1, 2010. http://www.theses.fr/2010BOR14189/document.
Testo completoAbstract (sommario):
Les interactions protéine-protéine jouent un rôle primordial dans de nombreux processus biologiques. L’importance de ces interactions a suscité le développement de nouvelles approches thérapeutiques qui ciblent ces complexes protéiques. Nous nous proposons d’inhiber ces interactions en élaborant une stratégie de reconnaissance de surfaces de protéines par des molécules synthétiques de taille intermédiaire, les foldamères d’oligoquinoline. Ces composés se replient en des structures hélicoïdales stables dont chaque élément constitutif peut être fonctionnalisé pour permettre des propriétés de reconnaissance de surface de protéine.Afin de valider ce concept, l’interaction entre l’anhydrase carbonique humaine de type II (HCAII) et son inhibiteur N-benzyl-4-sulphamoylbenzamide (SBB) a été sélectionnée comme système modèle. Plusieurs étapes de synthèse ont permis de concevoir de nouveaux foldamères capables de former un complexe avec l’enzyme par l’intermédiaire de l’inhibiteur SBB et d’un espaceur approprié. Chaque complexe protéine-foldamère a été co-cristallisé et l’affinité des interactions a été caractérisée par dichroïsme circulaire induit et par résonance plasmonique de surface. Ce concept a ensuite été appliqué à une interaction protéine-protéine d’intérêt thérapeutique, le complexe IL-4/IL-4R, dans le cadre du programme européenFOLDAPPI (FP7-PEOPLE-IAPP-2008)Protein-protein interactions play key roles in many biological processes as well as in many diseases. The importance of these interactions has led to the development of new therapeutic approaches that target protein interfaces. We have developed a protein surface recognition strategy to inhibit protein-protein interactions by using intermediate size organicmolecules called oligoquino line foldamers, that result in very stable and well defined helical structures. These helical backbones are used as templates within each building block can be modulated to allow protein surface recognition.In order to validate this concept, the well-characterized interaction between the enzyme human carbonic anhydrase II (HCAII) and its N-benzyl-4-sulphamoylbenzamide (SBB) inhibitor was selected as a model system. Multi-steps synthesis allowed functionalization of new foldamers able to bind to the enzyme through the SBB inhibitor attached by a spacer.Each foldamer–protein complex was cocrystallized and the affinity of the interactions was assayed using both induced circular dichroïsm and surface plasmon resonance. The concept of using a foldamer against protein-protein interaction was then applied to a protein complex of therapeutic interest, IL-4/IL-4R, within the European FOLDAPPI program (FP7-PEOPLEIAPP- 2008)
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Justad, Klara. "Karensregeln : Uppfyller den sitt syfte i 57 kap. 4 och 6 §§ IL?" Thesis, Högskolan i Jönköping, Internationella Handelshögskolan, 2010. http://urn.kb.se/resolve?urn=urn:nbn:se:hj:diva-13977.
Testo completoAbstract (sommario):
Ett fåmansföretags delägare beskattas i enlighet med speciella skatteregler vid utdelning och försäljning i 56 och 57 kap. Inkomstskattelag (1999:1229) (IL). Detta beror på att lagstift- ningen vill hindra att inkomster som egentligen är tjänsteinkomster beskattas i inkomstsla- get kapital, vilket kan hänföras den nära anknytning som delägarna anses ha med företaget. Dessa regler har kompletterats med stopplagsbestämmelser, vilka har som syfte att hindra att fåmansföretagsreglerna på olika sätt kringgås. Ett exempel på en stopplagsbestämmelse är den karensregel vilken återfinns i både 57 kap. 4 § IL och i 57 kap. 6 § IL. Karensregeln stadgar att om ett bolag har upphört att vara ett fåmansföretag eller då dess verksamhet har flyttats och bedrivs i ett annat fåmansföretag, skall bolagen omfattas av en karenstid om fem beskattningsår då fåmansföretagsreglerna fortsatt skall gälla. Angående 57 kap. 4 § IL har ett i år utkommet rättsfall, RÅ 2010 ref. 11, tolkat bestämmelsen. Syftet med uppsatsen är att utreda huruvida 57 kap. 4 och 6 §§ IL uppfyller de ändamål som bestämmelserna har getts. Slutsatsen om 57 kap. 4 § IL är att bestämmelsen har ansetts uppfylla de ändamål vilka be- stämmelsen getts. Det föreligger dock osäkerheter kring tolkningen av 57 kap. 4 § IL, vilket kan härledas dess otydliga utformning. Emellertid har Regeringsrätten i RÅ 2010 ref. 11 tolkat bestämmelsen på så sätt att det får anses att bestämmelsen numera uppfylla sitt syfte. Slutsatsen om 57 kap. 6 § IL är att bestämmelsen inte längre uppfyller det syfte som den hade vid införandet. Detta på grund att den träffar företag som på grund av företagseko- nomiska grunder inte längre anses som ett fåmansföretag. I dessa fall finns det inget kring- gående syfte bakom dessa förfaranden, vilket bestämmelsen är tänkt att stoppa upp.