Teses / dissertações sobre o tema "Inflammation Mediators"
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1
Farrell, Adrian J. "Mediators of synovial inflammation". Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.284326.
2
Woollard, Kevin J. "Mediators of monocyte activity in inflammation". Thesis, Aston University, 2003. http://publications.aston.ac.uk/11001/.
Resumo:
The effects of incubation of CRP with human primary and monocytic cell lines were examined using monocytic cytokine expression, adhesion molecule expression and adhesion to endothelial cells and intracellular peroxide formation, as end points. Monocytic intracellular signalling events were investigated after interaction of CRP with specific CRP receptors on monocytes. These initial signalling events were examined for their role in modulating monocyric adhesipn molecule and cytokine expression. Monocyte recruitment and retention in the vasculature is also influenced by oxidative stress. Therefore the effect of 6 weeks of antioxidant intervention in vivo was examined on monocytic adhesion molecule expression, adhesion to endothelial cells ex vivo and on serum CRP concentrations, pre- and post- supplementation with the antioxidants vitamin C and vitamin E. In summary, CRP is able to bind Fc?RIIa. CRP binding Fc?R initiates an intracellular signalling cascade that phosphorylates the non-receptor ryrosine kinase, Syk, associated with intracellular ryrosine activating motifs on the cytoplasmic tail of Fey receptors. CRP incubations increased phosphatidyl inositol turnover and Syk phosphorylation ultimately led to Ca2+ mobilisation in monocytes. CRP mediated Syk phosphorylation in monocytes leads to an increase in CD1 lb and IL-6 expression. CRP engagement with monocytes also leads to an increase in peroxide production, which can be inhibited in vitro using the antioxidants a-tocopherol and ascorbic acid. CRP mediated CDllb expression is not redox regulated by CRP mediated changes in cytosolic peroxides. The Fc?RIIa polymorphism at codon 131 effects the phenotypic driven changes described in monocytes by CRP, where R/R allotypes have a greater increase in CD1 lb, in response to CRP, which may be involved in promoting the monocytic inflammatory response. CRP leads to an increase in the expression of pro-inflammatory cytokines, which alters the immune phenotype of circulating monocytes. Vitamin C supplementation reduced monocytic adhesion to endothelial cells, but had no effect on serum levels of CRP.
3
Robinson, Emily. "Mediators of inflammation in acute neurotoxicity". Thesis, University of Manchester, 2013. https://www.research.manchester.ac.uk/portal/en/theses/mediators-of-inflammation-in-acute-neurotoxicity(a657668f-f6de-4fb6-878d-65846fc18e66).html.
Resumo:
Neuroinflammation is a major feature of most neurodegenerative conditions, and can leadto the exacerbation of neuronal injury. Inflammatory challenges in the central nervoussystem (CNS) have been shown to activate peripheral immune cells, which subsequentlyinfiltrate into the brain. Concurrently, resident inflammatory cells in the CNS, such asmicroglia, become activated and release inflammatory mediators, including cytokines.The pro-inflammatory cytokine interleukin-1 (IL-1) is a key mediator of neuronal injury.Although two IL-1 agonists exist, IL-1α and IL-1β, the majority of research has focussedon the contribution of IL-1β to neuronal injury. Excitotoxic cell death in the rat brain,induced by striatal injection of the glutamate agonist AMPA, is exacerbated by coadministrationof recombinant IL-1β. To identify possible mediators which facilitate theexacerbation of neuronal injury by IL-1 this study investigated the early peripheral andcentral mediators of inflammation in response to AMPA + IL-1β.Neutrophil infiltration and increased neuronal activity were found to be present at 4h post-AMPA + IL-1β injection, which lead to the induction of microglial IL-1α in the ipsilateralcortex, in the absence of any IL-1β expression. To target the peripheral neutrophil responsean intervention study was performed to inhibit peripheral TNFα, which is thought tomobilise neutrophils. No significant effect of pre-treatment with etanercept, a TNFαinhibitor, was observed on neuronal injury produced in response to AMPA + IL-1β, thougha slight trend for protection was seen. To target the central IL-1α response after AMPA +IL-1β treatment an anti-IL-1α antibody was injected directly into the cerebral cortex, butthis had no effect on AMPA + IL-1β induced cell death. Therefore, using a reductionist invitro approach in organotypic slice cultures haemin, an inducer of endogenous IL-1α, wasused to investigate IL-1α mediated cell death. Haemin induced cell death was shown to beIL-1 dependent and preliminary studies using IL-1αKO mice indicated that IL-1α maypartially mediate this effect. This suggests that in the AMPA + IL-1β paradigm IL-1α is thedominant IL-1 isoform early after AMPA + IL-1β treatment, which can trigger subsequentneuronal cell death, as a result of the additive effects of neutrophil infiltration and highneuronal activity in the cortex. This study highlights the potential therapeutic value ofinhibiting IL-1α expression early following acute neuronal injury.
4
Wesseldijk, Feikje. ""Inflammatory Soup" mediators of inflammation in CRPS". [S.l.] : Rotterdam : [The Author] ; Erasmus University [Host], 2008. http://hdl.handle.net/1765/13553.
5
McKay, Anne. "The role of immune mediators in airway inflammation". Thesis, University of Glasgow, 2004. http://theses.gla.ac.uk/4828/.
Resumo:
Asthma is a chronic inflammatory condition of the airways characterised by reversible airflow obstruction, airway hyper-responsiveness and inflammatory infiltrates in the airway walls containing eosinophils, T lymphocytes and mast cells. T helper (Th) lymphocyte subsets, defined by the cytokines they secrete, are thought to play a key role in the in the initiation and perpetuation of chronic airway inflammation. Th2 cells, producing interleukin (IL)-4, IL-5, IL-9 and IL-13, are thought to be of particular importance. In contrast, Thl cells producing interferon (IFN)-y may counteract the development of Th2 responses and so down-regulate the asthmatic response. The prevalence of asthma is increasing but the reasons for this are not fully understood. In addition, some patients do not respond adequately to treatment with corticosteroids, currently the most effective anti-inflammatory agents used routinely in human asthma. There is therefore continual interest in developing new therapeutic agents for asthma. A greater understanding of the regulation of inflammatory responses in asthma will assist in the identification of potential targets for therapeutic intervention. The aims of this thesis were (i) to assess the role of the cytokine IL-18 in allergic airway inflammation by determining IL-18 levels in induced sputum in asthmatic subjects in comparison to normal subjects, and by studies in a murine model of allergic asthma using IL-18 gene deficient mice and (ii) to assess the potential antiinflammatory actions of simvastatin and thymosin beta 4 sulfoxide in the murine asthma model. IL-18 is a pro-inflammatory cytokine which can promote IFN-y secretion and, in association with IL-12, enhance the development of Thl responses. However, in some circumstances it may also stimulate Th2 responses. IL-18 therefore has the potential to suppress or exacerbate allergic airway inflammation. The role of IL-18 in both clinical and experimental asthma remains unclear. Statins are inhibitors of the rate-limiting enzyme, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, in cholesterol biosynthesis. As such they have been widely used as cholesterol lowering agents in clinical practice. They have previously been shown to have anti-inflammatory properties independent of their cholesterol-lowering ability in clinical studies of atherosclerotic disease and in animal models of Thlmediated inflammation. Thymosin beta 4 sulfoxide (T~4S0) is a 5 kDa peptide. Intracellularly its principal activity is to regulate actin polymerization. Corticosteroid treatment of monocytes in vitro induces the release of T~4S0 extracellularly, where it can inhibit neutrophil chemotaxis. Exogenous administration of T~4S0 has been shown to reduce neutrophilic inflammation in animal models. In this study it is shown that IL-18 is detectable in induced sputum fluid and IL-18 mRNA is expressed in induced sputum cells from asthmatic and nOlmal subjects. IL- 18 protein levels in induced sputum, and IL-18 mRNA expression in induced sputum cells were not significantly different between these groups. IL-18 production was localised to sputum macrophages. However, cigarette smoking significantly reduced IL-18 levels in induced sputum fluid in both asthmatic and normal subjects. In asthmatics, but not normal subjects, the reduction in IL-18 levels in sputum fluid was associated with reduced IL-18 mRNA expression in induced sputum cells. A murine model of allergic asthma, using BALB/C mice sensitised and challenged with ovalbumin (OVA), was used to examine the role of IL-18 in allergic responses in vivo. IL-18 gene knockout (ko) had significantly reduced bronchoalveolar lavage (BAL) total cell count and eosinophilia compared to wild-type (WT) mice. IL-18 ko mice had reduced IL-4 expression in thoracic lymph nodes, as assessed by quantitative peR, and significantly reduced OVA-specific IL-4 secretion from thoracic lymph node cultures assessed by ELISA. Serum OVA-specific IgG 1, IgG2a and IgE and total IgE levels were not significantly different between IL-18 ko and WT mice. The murine model of allergic asthma was also used to examine the anti-inflammatory activities of simvastatin and T~4S0 in a Th2-mediated, eosinophilic condition. Simvastatin treatment, either orally or intraperitoneally, and T~4S0 intraperitoneally reduced the total inflammatory cell infiltrate and eosinophilia in BAL fluid in response to inhaled OV A challenge. At higher doses of simvastatin intraperitoneally, a histological reduction in inflammatory infiltrates in the lungs was observed. Treatment with simvastatin intraperitoneally, but not orally, and T~4S0 were also associated with a reduction in IL-4 and IL-5 levels in BAL fluid. OVA-induced IL-4 and IL-5 secretion was reduced in thoracic lymph node cultures from both simvastatin-treated and T~4S0-treated mice. Neither simvastatin nor T~4S0 treatment altered serum total IgE or OVA-specific IgG 1 and IgG2a levels. The results described show that IL-18 can be detected in the induced sputum fluid of asthmatic and normal subjects and that cigarette smoking significantly reduces its levels. Studies in a murine model of allergic asthma suggest that IL-18 has a proinflammatory role in allergic airway inflammation, at least in part through its ability to induce IL-4 secretion. Both simvastatin and thymosin beta 4 sulfoxide had convincing anti-inflammatory properties in the murine model of asthma used, and these agents, or related compounds, may have therapeutic potential in human asthma.
6
Wilson, Susan Jane. "Mucosal inflammation in allergic rhinitis". Thesis, University of Southampton, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295233.
7
李蕙琛 e Wai-sum Rachel Li. "Control of adenosine in human umbilical vein endothelial cells during inflammation". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39557479.
8
Airila-Månsson, Stella. "Progression of periodontitis and influence of periodontal bacteria on release of inflammatory markers in Swedish adults /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-622-0/.
9
Khan, Sarah Basir. "Mediators of inflammation and fibrosis in experimental crescentic glomerulonephritis". Thesis, Imperial College London, 2005. http://hdl.handle.net/10044/1/11303.
10
Porter, John Robert Stephen. "Microvesicles as mediators of inflammation in severe burn injury". Thesis, Imperial College London, 2015. http://hdl.handle.net/10044/1/43963.
Resumo:
The host response to a severe burn injury is characterised by exaggerated systemic inflammation. Early clinical manifestations include shock, respiratory failure, renal failure and immunosuppression. The signalling pathways that propagate the inflammatory response are unclear but have traditionally been thought to involve overspill of proinflammatory cytokines. The importance of microvesicles, sub-cellular membrane-bound particles, is increasingly being recognised in the context of intercellular communication. Although circulating microvesicles are elevated in proinflammatory states such as sepsis, their relevance to the post-burn inflammatory response has not previously been evaluated. We hypothesised that circulating microvesicles play a crucial role in propagating the post-burn inflammatory response. Our overall aims were to 1) optimise protocols for the processing and analysis of plasma samples for microvesicle content; 2) characterise the circulating microvesicle profile associated with severe burn injury; 3) develop in vitro techniques to assess microvesicle production and function. The major findings of this work were that microvesicles derived from leukocytes, neutrophils, monocytes and endothelial cells were significantly elevated within 24 hours of burn injury. Microvesicle levels fell rapidly and were significantly decreased by day two post-injury. Total leukocyte- and neutrophil-derived microvesicles were significantly higher in non-survivors of burn injury as compared to survivors. In vitro studies demonstrated that neutrophil microvesicle release could be elicited by incubation with opsonised heat-killed cells. Pilot analysis of burn patient samples, using an endothelial co-culture assay, suggested that microvesicles may regulate the innate immune response to burn injury. These findings indicated that circulating microvesicles are an important component of the post-burn inflammatory response. Their precise activity is likely to be subtype-specific but the association of neutrophil-derived microvesicles with patient outcome alludes to a key role in burn pathophysiology.
11
Andersson, Åsa. "Macrophages as central inflammatory mediators and as targets for therapeutic interventions /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-618-2/.
12
Djukanovic, Ratko. "Cellular and soluble mediators of mucosal inflammation in bronchial asthma". Thesis, University of Southampton, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.295878.
13
Bhagat, Kiran. "Vascular inflammation and its effects on endothelial and smooth muscle function, a study in healthy volunteers". Thesis, University College London (University of London), 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263301.
14
Baxter, Edith. "Potential mediators of the decrease in CYP1A activity during CNS inflammation". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape4/PQDD_0018/MQ57182.pdf.
15
Nicholson, Tara. "Potential mediators of the downregulation of cytochrome P450 during central inflammation". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ66639.pdf.
16
Pépin, Marion. "Caractérisation de nouveaux médiateurs entre cancer, inflammation et thrombose : ADAMTS13, PSGL-1 et Siglec-5". Thesis, Université Paris-Saclay (ComUE), 2016. http://www.theses.fr/2016SACLS571/document.
Resumo:
La maladie cancéreuse et la maladie thrombotique sont des problématiques fréquentes et graves rencontrées en pathologie humaine et en santé publique. Elles ont une relation réciproque médiée par des interactions cellulaires et des mécanismes moléculaires complexes faisant intervenir des acteurs de l’hémostase et de l’immunité. Tout ou partie de ces phénomènes rendent en effet compte du processus d’inflammation et de réponse de l’organisme à l’agression. La caractérisation de certains médiateurs moléculaires ayant des rôles connus dans l’hémostase et l’inflammation peut nous permettre d’améliorer la compréhension de ces phénomènes et de proposer des pistes de réflexion diagnostiques ou thérapeutiques.Nous nous sommes donc intéressé au couple facteur Willebrand/ADAMTS13 : une protéine clé de l’hémostase dont le taux est influencé par les processus inflammatoires et sa protéase régulatrice. Cette étude menée chez des patients atteints de cancer nous a permis de montrer que l’utilisation de ces protéines comme des biomarqueurs peut améliorer la stratification du risque individuel de thrombose pour les patients et donc d’améliorer la prise en charge thérapeutique. Le rôle de ces protéines dans la physiopathologie de ces mécanismes reste à préciser.Par ailleurs, sur la base de connaissances structurelles, nous avons l’émis l’hypothèse d’une interaction entre deux récepteurs de la surface des leucocytes, cellules-clés de la réponse inflammatoire. En effet, PSGL-1 (P-sélectine glycoprotéine ligand 1), récepteur présent sur une grande partie des leucocytes est le ligand de la P-sélectine sur l’endothélium vasculaire et joue un rôle majeur dans le roulement des leucocytes permettant leur recrutement aux sites de l’inflammation. PSGL-1 a une structure riche en acides sialiques. Le Siglec-5 est quant à lui un récepteur de structure proche des immunoglobulines qui lie des acides sialiques. Nous avons donc décrit et caractérisé la liaison entre ces deux protéines, et étudié son rôle dans le roulement des leucocytes in vitro et in vivo. Avant d’envisager toute application, il reste bien sûr à caractériser plus précisément les modalités de cette interaction (site de liaison, etc…) et son effet dans d’autres mécanismes régulés par l’interaction PSGL-1/P-sélectine comme la formation du thrombusCancer and thrombosis are frequent and serious concerns in human pathology and public health. This conditions are known to share closed relationships, and reciprocal promotion involving cellular interactions and complex molecular mechanisms. Molecular pathways often involve hemostasis or immunity actors and participate in inflammation process, which can be either cause or consequence. Improved knowledge on molecular mediators at the crossroads of hemostasis and inflammation may allow best understanding of these mechanisms and improving therapeutic management.Thus, we studied Willebrand factor / ADAMTS13 couple : a key protein in hemostasis whose rate is influenced by inflammatory processes and its regulatory protease. This study in cancer patients shows that Willebrand factor and ADAMTS13 could be used as biomarkers to predict individual thrombosis risk and thus improve therapeutic management. Precise role of this proteins in cancer-mediated thrombosis remain unexplored.Furthermore, we hypothesized an interaction between two leukocyte receptors : PSGL-1(P-selectin glycoprotein ligand-1) and Siglec-5. Leukocytes, especially neutrophils are recruited to inflammation sites after a key step of rolling along vasculature. PSGL-1 expressed on the majority of leukocytes is P-selectin ligand and plays a major role in leukocyte rolling. PSGL-1 has a structure rich in sialic acids. Siglec-5 is an immunoglobulin-like receptor and binds sialic acids. Thus, we described and characterized the interaction between these two proteins, and studied its role in leukocyte rolling in vitro and in vivo. Before considering any application, the modalities of this interaction should further analyzed (binding site, etc. ...) and its effect in other mechanism involving PSGL-1/P-selectin interaction like thrombus formation
17
Hasan, Hisham Ahmed. "The effects of glucocorticoids and other pharmacological agents on the production of cytokines and prostaglandin Eâ†2 by human cells in vitro". Thesis, University of Sheffield, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.265572.
18
Fehrenbacher, Jill Christine. "The contribution of inflammation and inflammatory mediators to sensitization of sensory neurons". [Bloomington, Ind.] : Indiana University, 2005. http://wwwlib.umi.com/dissertations/fullcit/3183931.
Resumo:
Thesis (Ph.D.)--Indiana University, 2005.Source: Dissertation Abstracts International, Volume: 66-07, Section: B, page: 3648. Chairperson: Michael R. Vasko. Title from dissertation home page (viewed Oct. 5, 2006).
19
Li, Shun. "Crosstalk between mediators of inflammation and the IGF axis in liver metastasis". Thesis, McGill University, 2011. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=104626.
Resumo:
Liver metastases are a frequent and often fatal occurrence in cancer patients. A better understanding of the biology of liver metastasis is essential to improve survival statistics for these patients. Although the contribution of IGF-IR to malignancy has been recognized for over 2 decades, the role that the IGF axis plays in metastasis is not yet fully understood. Using a murine Lewis lung carcinoma-based model, our laboratory has previously shown that the IGF-I receptor (IGF-IR) plays the key role in liver metastasis by regulating matrix metalloproteinase (MMP) expression and by increasing tumor cells survival and proliferation in the liver. The objectives of my project were to further analyze IGF-mediated regulation of MMP expression and investigate the crosstalk between the IGF axis and mediators of inflammation, particularly the TNF-alpha/NF-kappaB axis. My results revealed the following: A. In M-27 cells with ectopic IGF-IR overexpression (M-27IGFIR) that have acquired a liver-metastasizing potential but lost the ability to colonize the lung, PKC-alpha was found to be transcriptionally down-regulated and this resulted in decreased expression of the PKC-regulated MMPs- MMP-9, MMP-3 and MMP-13. This altered MMP expression could account for the changes in site-specificity of metastasis observed in these cells. B. In M-27IGFIR, but not in wild type M-27 cells, TNF-alpha was found to induce IL-6 production and autocrine IL-6/gp130/STAT3 signalling and thereby provide a mechanism of escape from the pro-apoptotic effects of this inflammatory cytokine. When this escape mechanism was abrogated by the use of siRNA or neutralizing antibodies, the cells re-acquired their sensitivity to apoptosis and their metastatic ability was reduced, indicating that it played a critical role in liver-metastasis in vivo. C. A mechanism of synergistic crosstalk between IGF and TNF signalling was identified in cells with high IGF-IR expression levels. In these cells, NF-kappaB activation in response to TNF-alpha was found to be accelerated in a PI3-K/Akt –dependent manner, identifying IGF-IR as an enhancer of NF-kappaB signalling and suggesting that cytokine expression, in particular IL-6 production may be regulated by the kinetics of NF-kappaB activation. Together, these results identify novel molecular mechanisms that mediate the diverse effects of IGF-IR on the tumor microenvironment and on metastasis and may be targeted for anti-cancer therapy. Les métastases hépatiques sont souvent mortelles dans les patients atteint du cancer. Une meilleure compréhension de la biologie des métastases hépatiques nous aiderais a amélioré le taux de survie des ces patients. Cela fait plus de vingt ans que la contribution de IGF-IR dans la progression du cancer est reconnue, mais nous ne savons pas encore exactement comment. Utilisant le modèle de carcinome pulmonaire de Lewis, nous avons déjà démontré que le IGF-IR régularise l'expression des métalloprotéinases matricielles (MMP) et ainsi joue un rôle important dans les métastases hépatiques. Les objectifs de mon projet étaient d'analyser le mécanisme de régulation des MMPs par IGF et d'examiner la diaphonie de signaux entre l'axe IGF et les médiateurs d'inflammations, en particulier TNF-α et NF-κB. Mes résultats démontrent ceci: A. Dans les cellules M27 transfectées avec le IGF-IR (M-27IGFIR) et qui ont acquis l' habileté de métastasier au foie mais on perdu leur potentiel de coloniser les poumons, l'expression transcriptionnelle de PKC-α était diminuée, résultant en une diminution de l'expression des MMPs qui sont régularisées par PKC-α: MMP-1, MMP-3 et MMP-13. La variation de profil de MMP de ces cellules pourrait expliquer le changement de site de métastases de ces cellules. B. Dans les cellules M-27IGFIR, mais pas dans les cellules sauvages M27, TNF-α peut induire la production de IL-6 et des signaux autocrines via la voie de transduction IL-6/gp-130/STAT3. De cette façon, les cellules peuvent évader les effets pro-apoptotiques de IL-6. Quand nous avons inhibé cette voie de signalisation en utilisant un siRNA et des anticorps, les cellules ont re-acquis leur habileté d'induire l'apoptose et leur habilité de métastasier a été réduit. Ces résultats démontrent que cette voie de signalisation est importante pour les métastases hépatiques des cellules M-27IGFIR. C. Dans les cellules avec une haute expression de IGF-IR, j'ai identifié un échange de signaux entre les voies de signalisation de IGF et TNF. Dans ces cellules, l'activation de NF-κB, suivant la stimulation avec TNF-α, a été accélérée d'une manière dépendante de la voie de signalisation PI3K/Akt. Ces résultats démontrent que IGF-IR augmente la signalisation de l'agent de transcription NF-κB et suggère que l'expression des cytokines, IL-6 en particulier, peut être régulée par l'activation de NF-κB. Conjointement, mes résultats identifient de nouveaux mécanismes, dont IGF-IR, jouant un rôle dans le microenvironment des tumeurs, dans la métastase et introduit des cibles pour la thérapie.
20
Coras, Roxana Georgiana. "Identification of Metabolites as Biomarkers and Mediators of Inflammation in Inflammatory Arthritis". Doctoral thesis, Universitat Autònoma de Barcelona, 2021. http://hdl.handle.net/10803/673867.
Resumo:
L’artritis inflamatòria representa una gran càrrega social i econòmica tot i els recents avenços terapèutics. Malgrat un millor coneixement dels mecanismes patogénics, l’elecció de l’tractament encara es realitza a manera de prova, el que condueix a una manca de control de l’activitat de la malaltia en aproximadament el 30% dels pacients i una alta taxa d’efectes secundaris. La identificació de mediadors de malaltia i predictors de resposta a el tractament és necesaria per permetre el tractament adequat i aconseguir la remissió clínica o al menys una baixa activitat de la malaltia. És poc prob-able que un sol biomarcador proporcioni informació suficient per explicar aquestes malalties heterogènies. La metabolòmica és una eina que es pot utilitzar per al descobriment de biomarcadors, ja que pot identificar perfils d’una gran quantitat de metabòlits en diferents tipus de mostres. Els metabòlits no són només el resultat final dels processos químics que tenen lloc en la cèl·lula, sinó que també juguen un paper crític en una varietat de processos cel·lulars, com les modificacions postranslacionals i la regulació de les cèl·lules immunes. Amb la hipòtesi que els metabòlits circulants reflecteixen processos sinovials, aquest projecte va tenir com a objectiu estudiar els metabòlits circulants en relació amb l’activitat de la enfermedad y la resposta als fàrmacs antireumàtics modificadors de la malaltia. Descrivim diferents perfils metabolòmics en pacients amb artritis inflamatòria comparats amb controls. També identifiquem metabòlits que es correlacionen amb l’activitat de la malaltia i que poden ser mediadors de la malaltia, així com metabòlits associats amb la resposta a el tractament.La artritis inflamatoria representa una gran carga social y económica a pesar de los recientes avances terapéuticos. A pesar de un mejor conocimiento de los mecanismos patogénicos, la elección del tratamiento todavía se realiza a modo de prueba, lo que conduce a una falta de control de la actividad de la enfermedad en aproximadamente el 30 % de los pacientes y una alta tasa de efectos secundarios. La identificación de mediadores de enfermedad y predictores de respuesta al tratamiento es necesaria para permitir el tratamiento adecuado y lograr la remisión clínica o al menos una baja actividad de la enfermedad. Es poco probable que un solo biomarcador proporcione información suficiente para explicar estas enfermedades heterogéneas. La metabolómica es una herramienta que se puede utilizar para el descubrimiento de biomarcadores, ya que puede identificar perfiles de una gran cantidad de metabolitos en diferentes tipos de muestras. Los metabolitos no son solo el resultado final de los procesos químicos que ocurren en la célula, sino que también juegan un papel crítico en una variedad de procesos celulares, como las modificaciones postranslacionales y la regulación de las células inmunes. Con la hipótesis de que los metabolitos circulantes reflejan procesos sinoviales, este proyecto tuvo como objetivo estudiar los metabolitos circulantes en relación con la actividad de la enfermedad y la respuesta a los fármacos antirreumáticos modificadores de la enfermedad. Describimos diferentes perfiles metabolómicos en pacientes con artritis inflamatoria comparados con controles. También identificamos metabolitos que se correlacionan con la actividad de la enfermedad y que pueden ser mediadores de la enfermedad, asi como metabolitos asociados con la respuesta al tratamiento.
Inflammatory arthritis represents a great social and economic burden despite recent therapeutic advances. Although we have a better understanding of the pathogenic mechanisms, treatment election is still made on a trial basis, which leads to lack of control of disease activity in approximately 30% of patients and a high rate of side effects. The identification of disease mediators and predictors of response to treatment are needed to allow the adequate treatment and achieve clinical remission or at least low disease activity. A single biomarker is unlikely to provide sufficient information to explain these heterogeneous diseases. Metabolomics is a tool that can be used for biomarker discovery as it can identify profiles of a large number of metabolites in different types of samples. Metabolites are not just the end result of chemical processes that occur in the cell, but also play critical role in a variety of cellular processes, such as post-translational modifications and immune cell regulation. With the hypothesis that circulating metabolites reflect synovial processes, this project aimed to study circulating metabolites in relation to disease activity and response to disease modifying anti- rheumatic drugs. We described different metabolomic profiles in patients with inflammatory arthritis compared to controls. We also identified metabolites that correlate with disease activity and that may be mediators of disease, as well as metabolites that are associated with response to treatment.
Universitat Autònoma de Barcelona. Programa de Doctorat en Medicina
21
Fredriksson, Lars. "Local and systemic inflammatory mediators and their relation to pressure-pain threshold and pain of the temporomandibular joint /". Stockholm, 2006. http://diss.kib.ki.se/2006/91-7140-876-2/.
22
Mullins, Gail E. "Studies of high mobility group box chromosomal protein 1 as a pro-inflammatory cytokine /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-333-7/.
23
Bao, Lei. "Immunomodulation and immunopathogenesis in the autoimmune disease with emphasis on autoimmune neuritis and arthritis /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-447-X/.
24
Loo, Tjing Yung, e 魯慶榮. "Profiles of cytokines and inflammatory mediators: implications in periodontal assessment". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2011. http://hub.hku.hk/bib/B45893305.
25
Abelin, Törnblom Susanne. "Mediators of cervical ripening in preterm birth : experimental and clinical investigations /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-305-1/.
26
Lau, Yuen-chi Roy, e 劉源智. "Role of cyclooxygenases in monocrotaline induced pulmonary injury". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2004. http://hub.hku.hk/bib/B45010146.
27
Pak, Anne. "The influence of inflammation and inflammatory mediators on p-glycoprotein expression in rats". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0024/MQ40858.pdf.
28
Ford, Louise. "Wolbachia mediators of inflammation and their role in the immune response to filariasis". Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.273984.
29
Kim, Sungwon. "Functional Characterization of the Avian Inflammatory Mediators Nod1, MIF and IL-22". Diss., Virginia Tech, 2011. http://hdl.handle.net/10919/77232.
Resumo:
Inflammation can be initiated by an innate immune sensor, followed by activation of a signal mediator, resulting in control of immune response by a signal regulator. Mammalian nucleotide-binding oligomerization domain protein 1 (Nod1) and Nod2 initiate host innate immune response by recognition of specific bacterial molecules, resulting in the production of pro-inflammatory cytokines, chemokines, and anti-microbial peptides. A candidate sequence of chicken Nod1 (ChNod1) was identified with no current evidence of ChNod2. Stimulation of transiently overexpressed ChNod1 and its mutants with mammalian Nod-specific ligands was not conclusive of the function of ChNod1 most likely due to self-activation of ChNod1. In vitro studies showed no significant difference in expression of Nod1, its signaling molecules and pro-inflammatory cytokines in stimulated chicken mononuclear cells with synthetic ligands for mammalian Nod1 or Nod2.
A signal mediator, macrophage migration inhibitory factor (MIF) inhibits the random migration of macrophages. Chemotaxis assay using recombinant ChMIF (rChMIF) revealed a substantial decrease in migration of macrophages. qRT-PCR analysis revealed that the presence of rChMIF enhanced levels of IL-1β and iNOS during monocytes stimulation with LPS. Additionally, Con A-stimulated lymphocytes exhibited enhanced IFN-γ and IL-2 transcripts in the presence of rChMIF.
IL-22, which may act as a signal regulator, is an important effector of activated Th1 and Th17 as well as natural killer cells during inflammation. Recombinant ChIL-22 alone did not have an impact on chicken embryo kidney epithelial cells (CKECs); however, co-stimulation of CKECs with LPS and rChIL-22 enhanced the production of pro-inflammatory cytokines and anti-microbial peptides. Furthermore, rChIL-22 alone stimulated acute phase reactants in chicken embryo liver cells. These effects of rChIL-22 were abolished by addition of rChIL22 binding protein. Taken together, these results indicate an important role of ChIL-22 on epithelial cells and hepatocytes during inflammation.
In this project, we identified and characterized the avian inflammatory mediators ChNod1, ChMIF, and ChIL-22. Studying each of their biological function in avian inflammation, especially under pathogenic challenges in epithelial tissues will provide a foundation for understanding the role of these inflammatory mediators in mucosal immunity.Ph. D.
30
Tsaprouni, Loukia G. "Histone acetylation and inflammatory mediators in inflammatory bowel disease". Thesis, University of Bedfordshire, 2003. http://hdl.handle.net/10547/620761.
Resumo:
During cell activation the tightly compacted DNA is made available to DNA-binding proteins allowing the induction of gene transcription. In the resting cell, DNA is packaged into chromatin whose fundamental subunit is the nucleosome, composed of an octamer of four core histones (H) 3, 4, 2A and 2B. During the induction of gene transcription, modification of histones, by acetylation, methylation etc., results in unwinding of the DNA, permitting access of large DNAbinding proteins, such as RNA polymerase II, and subsequent induction of gene transcription. This investigation initially examined the effects of pro-inflammatory stimuli LPS and TNF-a on the production of IL-8 in a macrophage cell line (U937 cells) and in two T-cell lines (Jurkat and HUT-78 cells) as a marker of NF-KB-directed inflammatory gene expression. The ability of dexamethasone (Dex) and triamcinolone acetonide (TA) (synthetic glucocorticoid agonists) to suppress expression of the inflammatory cytokine IL-8 and to regulate histone acetylation was also investigated in these cells. LPS and TNF-a caused an increase in IL-8 expression, which was further enhanced by the histone deacetylases inhibitor trichostatin A (TSA), suggesting a role for histone acetylation in IL-8 production in these cells. Dex and TA, repressed LPS- and TNF-a -induced IL-8 expression in all three cell lines. This effect of both Dex and TA was attenuated by TSA in all cell lines studied, where the effect of TSA was greater in TA stimulated cells. Stimulation of all cell lines with LPS and TNF-a induced acetylation of H4 lysine residues (K5, 8, 12 and 16), the highest elevation of which was for K8 and K12. Also demonstrate is a K5 and K16 specificity of acetylation by glucocorticoids, apparent in all cell lines studied. Dex and, to a greater extent, TA suppressed LPS- and TNFa-induced K8 and K12 acetylation. TSA attenuated the inhibitory effect of the glucocorticoids for all three cell lines. An inCrease in HDAC activity with GCs was observed and ChiP assay showed these events occur on the native IL-8 promoter via histone acetylation. Further studies investigated whether there were any links between histone acetylation and the regulation of apoptosis. It was showed that TSA induced apoptosis in cells previously stimulated with the inducer of oxidative stress hydrogen peroxide (H20 2). Studies into the activation of caspase 3 in LPS- and TNF-a stimulated cells revealed that the combinatory effect of Dex or TA with TSA Significantly enhanced expression of the marker in all three cell lines. In resting cells, Dex, and TA, in the presence of TSA downregulated caspase 3 expression. These findings support the notion that glucocorticoid actions on apoptosis is mediated, at least in part, through an action on histone acetylation. Finally, histone acetylation was investigated in vivo in two rat models of inflammation and in human subjects with inflammatory bowel disease (IBD). The results showed an increase in histone H4 acetylation lysine specificity of acetylation on K8 and K12 in inflamed tissue and Peyer's patches in animal models and in IBD patients. Whereas H3 acetylation was not elevated to the same extent in tissue and was restricted to the mantle zone of Peyer's patches. In general, the present studies on histone acetylation and inflammation (in animal models and IBD patients) underlined the possibility of a general mechanism linking activation of the transcription factor NFKB with histone acetylation. The ultimate objective of this work is to aid in the understanding of the mechanisms of how deregulation of chromosome structure leads to progression of the disease state. This knowledge may aid in the development of new therapeutic approaches or improved glucocorticoids.
31
Faull, Randall James. "Studies of vascular endothelial cell surface antigens relevant to the alloimmune response". Title page, table of contents and abstract only, 1991. http://web4.library.adelaide.edu.au/theses/09PH/09phf2634.pdf.
Resumo:
Bibliography: leaves 234-314. Examines the role of vascular endothelial cells in inflammation with particular reference to their participation in the immune response directed against a vascularised allograft (kidney)
32
AL-Hashimi, Najat AL-Sayed. "Experimental studies on effects of orthodontic forces in generation of immune responses : possible roles for immunoregulating molecules in the control of alveolar bone remodeling /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-985-4/.
33
Perkins, Douglas Jay. "Soluble mediators of inflammation and their effect on cyclooxygenase-2: Implications in preterm labor /". The Ohio State University, 1997. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487943610782714.
34
Nopp, Anna. "Characterisation of eosinophil activity markers : relation to allergic inflammation and apoptosis /". Stockholm : Karolinska Univ. Press, 2002. http://diss.kib.ki.se/2002/91-7349-129-2.
35
Hamawy, Majed Mahmood. "Antigen induced modulation of autonomic nervous system responses in immunoglobulin-E - sensitized rabbit lung". Diss., The University of Arizona, 1988. http://hdl.handle.net/10150/184590.
Resumo:
The major objective of this project was to examine the potential for mediators of IgE-mediated allergic reactions to alter neural activity. The project was divided into three parts. In Part I, the ability of endogenously released chemical mediators to alter neural activity in vitro was assessed by measuring isometric contractile responses to electrical field stimulation (EFS) (2-128 Hz, 20 V, 0.5 msec. duration) of sensitized rabbit bronchi before and after exposure to the antigen horseradish peroxidase (HRP). Antigen enhanced bronchial responses to EFS with low frequencies: mean log (± S.E.) frequency which produced 20% of maximum response decreased from 1.04 (± 0.05) to 0.90 (± 0.07) Hz (p < 0.05). Responses of unsensitized bronchi were not enhanced by antigen. Chlorpheniramine, an H₁ antagonist, abolished the antigen effect. Antigen did not enhance the responses to exogenous acetylcholine. Hence, the antigen is apparently modulating neural activity and not smooth muscle per se. In Part II, the capacity for histamine to modulate vagally-induced bronchoconstriction in anesthetized, vagotomized, mechanically-ventilated rabbits was examined in vivo. Changes in pulmonary resistance induced by electrically stimulating the cut ends of the vagi (2-32 Hz, 20 V, 0.5 msec. duration) were assessed before and 10 minutes after histamine aerosolization (10 breaths of 10 mg/ml). Histamine inhalation potentiated vagally-induced bronchoconstriction at low frequencies: mean log (± S.E.) frequency producing a 20% change in pulmonary resistance decreased from 0.88 (± 0.09) to 0.56 (± 0.15) (p < 0.05). Chlorpheniramine abolished this effect. In Part III, the dependence on IgE antibodies of the in vitro modulation of neurally-induced contraction of sensitized bronchi was investigated. Rabbits were passively immunized with fractions enriched with HRP-specific IgE, IgG, or IgM antibodies. After 72 hours, rabbits were sacrificed and the responses of bronchi to EFS were assessed before and after antigen challenge. Antigen enhanced the responses to EFS only of bronchi passively sensitized with IgE. Therefore, antigen enhancement of neural activity was dependent on IgE. These studies demonstrate that the interaction between antigen and IgE antibodies can induce the release of chemical mediators which can alter neural activity.
36
Harkin, Damien Gerard. "Morphological responses of neutrophils in suspension to plasma components and chemotactic factors /". Title page, contents and summary only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phh282.pdf.
37
Redington, Anthony Edward. "Fibrogenic mediators in atopic asthma : expression of endothelin, transforming growth factor-beta and basic fibroblast growth factor". Thesis, University of Southampton, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242665.
38
Moore, Andrea Rossi. "COX-2 inhibition impaired resolution of chronic inflammation in a murine model of autoimmune arthritis". Diss., Temple University Libraries, 2010. http://cdm16002.contentdm.oclc.org/cdm/ref/collection/p245801coll10/id/81890.
Resumo:
Microbiology and ImmunologyPh.D.
Rheumatoid arthritis (RA) is a chronic disease characterized by cycles of inflammation and resolution. Previously, it was believed that the resolution of inflammation is simply dissipation of pro-inflammatory signals, although current research indicates that resolution is an active process. Acute inflammation follows defined phases of induction, inflammation and resolution, and resolution occurs by an active process that requires COX-2 activity. This study aims to address whether this paradigm extends to a recognized model of chronic inflammation. We demonstrated in murine collageninduced arthritis that chronic inflammation follows the same sequential course. While there is the normal production of pro-inflammatory cytokines during inflammation and anti-inflammatory mediators such as 15-deoxyΔ12,14PGJ2 (15d-PGJ2) during resolution, interestingly there is sustained production of both COX-2 and the presumably proinflammatory PGE2 during both phases. Blocking COX-2 activity and therefore production of PGE2 during the resolution phase perpetuated instead of attenuated inflammation. Repletion with PGE2 analogs restored homeostasis, and this function is mediated by the pro-resolving lipoxygenase metabolite, lipoxin A4 (LXA4), which is a potent stop signal. Thus, the study provided in vivo evidence for a natural, endogenous link between the cyclooxygenase-lipoxygenase pathways and showed that PGE2 serves as a feedback inhibitor essential for limiting chronic inflammation in autoimmune arthritis. These findings may explain the enigma regarding why COX-2 inhibitors are palliative rather than curative in humans because blocking resolution may mitigate the benefit of preventing induction.
Temple University--Theses
39
McDaniel, J., Karen A. Massey e Anna Nicolaou. "Fish oil supplementation alters levels of lipid mediators of inflammation in microenvironment of acute human wounds". Wiley, 2010. http://hdl.handle.net/10454/4577.
Resumo:
noChronic wounds often result from prolonged inflammation involving excessive polymorphonuclear leukocyte activity. Studies show that the omega-3 polyunsaturated fatty acids eicosapentaenoic and docosahexaenoic acids found in fish oils generate bioactive lipid mediators that reduce inflammation and polymorphonuclear leukocyte recruitment in numerous inflammatory disease models. The purpose of this study was to test the hypotheses that boosting plasma levels of eicosapentaenoic and docosahexaenoic acids with oral supplementation would alter lipid mediator levels in acute wound microenvironments and reduce polymorphonuclear leukocyte levels. Eighteen individuals were randomized to 28 days of either eicosapentaenoic + docosahexaenoic acid supplementation (Active Group) or placebo. After 28 days the Active Group had significantly higher plasma levels of eicosapentaenoic (p<0.001) and docosahexaenoic acid (p<0.001) than the Placebo Group and significantly lower wound fluid levels of two 15-lipoxygenase products of omega-6 polyunsaturated fatty acids, [9- hydroxyoctadecadienoic (HODE) acid (p = 0.033) and15-hydroxyeicosatrienoic acid (HETrE) (p = 0.006)], at 24 hours post wounding. The Active Group also had lower mean levels of myeloperoxidase, a leukocyte marker, at 12 hours and significantly more re-epithelialization on Day 5 post wounding. We suggest that lipid mediator profiles can be manipulated by altering polyunsaturated fatty acid intake to create a wound microenvironment more conducive to healing.
40
Nist, Marliese Dion. "Inflammatory Mediators of Stress Exposure and Neurodevelopment in Very Preterm Infants". The Ohio State University, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=osu1565718071063954.
41
Blaho, Victoria Alison. "Lipid mediators in the development and resolution of experimental lyme arthritis". Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4819.
Resumo:
Thesis (Ph. D.)--University of Missouri-Columbia, 2007.The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. "May 2007" Includes bibliographical references.
42
Sylvin, Helena. "Allergen-induced airway reactions in the pig in vivo : inflammatory mediators as targets for asthma therapy /". Stockholm : [Karolinska institutets bibl.], 2002. http://diss.kib.ki.se/2002/91-7349-157-8.
43
Malamis, Dimitrios. "Systemic levels of inflammatory mediators in periodontitis". The Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1436961245.
44
Ehrs, Per Olof. "Quality of life and markers of inflammation : a study of asthma in primary care /". Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-539-9/.
45
Moëll, Annika. "Inflammatory mediators and enterovirus infections in human islets of Langerhans /". Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8501.
46
Hosseini, Abolfazl. "Nitric oxide : a marker for inflammation in the lower urinary tract /". Stockholm, 2004. http://diss.kib.ki.se/2004/91-7349-920-X/.
47
Van, de Vyver Mari. "The contribution of inflammatory mediators to delayed secondary muscle damage". Thesis, Stellenbosch : Stellenbosch University, 2013. http://hdl.handle.net/10019.1/79787.
Resumo:
Thesis (PhD)--Stellenbosch University, 2013.ENGLISH ABSTRACT: Background: Understanding the contribution of divergent individual response patterns remains a key objective in identifying mechanisms of inflammation and potential factors limiting the resolution of inflammation. The purpose of this research project was to investigate downstream effects of inflammation following exercise-induced muscle damage in human subjects. Methods: For three different studies, a total of 53 untrained healthy male participants were recruited and divided into a non-exercising control (n=13) and exercise-induced muscle damage groups (n=40). The study design for the three studies was the same (with few exceptions): Downhill running (DHR) (12 x 5min bouts, 10% decline, 15 km.h-1) with blood samples taken pre, post, after 2 and 4 hours post-exercise (2h, 4h) and on days 1, 2, 3, 4 and 7 (d1-d7). Serum was analysed for creatine kinase activity (CK), myoglobin (Mb), cortisol, cytokine (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokine (G-CSF, MIP-1β) and adhesion factor (sICAM-1, sP-selectin) concentrations. Tissue degradation was assessed by serum matrix metalloprotease (MMP-9) and myeloperoxidase (MPO) content. White blood cell differential count was determined and the surface expression of various cluster of differentiation factors (CD11b, CD163, CD68, CD88, CD34) as well as intracellular MPO were assessed in whole bood using flow cytometry. Nuclear localization of the inflammatory mediator NFĸB in isolated perhipheral blood mononuclear cells (PBMCs) was determined using immunofluorescence microscopy. Muscle biopsies (vastus lateralis) taken at baseline, 4h, d1 and d2 were analysed for fibre type, inflammatory and stress-induced pathways (STAT3, IĸBα, p38MAPK), myogenic factors (MyoD, myogenin), neutrophil activity (MPO) and satellite cell number (Pax7). Results: Participants in the DHR group were subdivided into those with a normal recovery (DHR1) and those who developed secondary damage (DHR2). CK peaked on d1 in both subgroups (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) and again on d4 only in the DHR2 group (1110 ± 184 u.L-1). A similar IL-6 and IL-10 response was evident immediately post DHR in all individuals. Additional IL-6 was released in the DHR2 subgroup peaking at 4h (10.3 ± 4.2 pg.mL-1) whereas IL-10 had returned to baseline. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) and CD163+ (3%) monocytes were significantly higher in the DHR2 subgroup. Neutrophil count at 2h (DHR1: 8.6 ± 0.8 x109 cells.L-1, DHR2: 11.4 ± 1.8 x109 cells.L-1) was significantly (p<0.02) correlated to CK activity on d4. PBMC NFĸB p65 nuclear localization was slightly less at 2h in the DHR2 compared to the DHR1 and control groups. Intramuscular STAT3 signalling and MPO were significantly higher in the DHR2 compared to the DHR1 subgroup at 4h and d2 respectively. The progenitor cell response was similar for all DHR individuals with an increase in Pax7+ SC observed at 4h (0.06 ± 0.01 Pax+ SCs/fibre) and d1 (0.07 ± 0.02 Pax+ SCs/fibre). Conclusion: Healthy young men can be divided into those with a adequate and those with a less efficient capacity to control the post damage inflammatory response. The early cytokine response, especially IL-6, seems to be a key role player in the cascade of events leading to late secondary skeletal muscle damage.
AFRIKAANSE OPSOMMING: Agtergrond: Die begrip van uiteenlopende individuele reaksie patrone, is belangrik in die identifisering van faktore asook meganismes betrokke in die ontwikkeling en resolusie van inflammasie. Die doel van hierdie navorsingsprojek was om die gevolge van oefening-geïnduseerde spierskade en inflammasie te ondersoek in menslike proefpersone. Metodiek: ‘n Totaal van 53 gesonde mans is tydens drie verskillende studies, gegroepeer in ’n kontrole (geen oefening) (n=13) en oefening geinduseerde spier skade (DHR) groep (n=40). Die uitleg van de studies was eenders (met min uitsonderings): Afdraende hardloop (12 x 5min hardloop sessies, 10% afdraende, 15km.h-1) met bloed monsters geneem voor, na, 2 ure, 4 ure (pre, post, 2h, 4h) en op dag 1, 2, 3, 4 en 7 (d1-7). Serum is ontleed vir die volgende: kreatien kinase aktiwiteit (CK), kortisol, sitokiene (TNFα, IL-1ra, IL-1β, IL-4, IL-6, IL-8, IL-10, sIL-6R), chemokien (G-CSF, MIP-1β) en adhesie molekuul (sICAM-1, sP-selectin) konsentrasies. Weefsel degradasie is vasgestel deur die teenwoordigheid van matriks metalo-protease-9 (MMP-9) en miëloperoksidase (MPO) in serum te meet. Differensiële witbloed sel (WBC) telling asook die teenwoordigheid van sekere differensiasie faktore (CD11b, CD163, CD68, CD88, CD34) op die sel oppervlak asook intrasellulêre MPO vlakke is bepaal deur gebruik te maak van vloeisitometrie. Die lokalisering van NFĸB in die selkerne van geïsoleerde bloed mononukleêre selle (PBMC) is bepaal deur fluoriserende mikroskopie. Spierbiopsies (vastus lateralis) geneem tydens rus (basislyn), na 4h, en op d1 en d2 is ontleed vir veseltipe, inflammatoriese en stresverwante faktore (STAT3, IĸBα, p38 MAPK), miogeniese faktore (myoD, myogenin), neutrofiel aktiwiteit (MPO) en aantal satelliet selle (Pax7). Resultate: Deelnemers in die DHR-groep is onderverdeel in twee groepe. Persone wat normaalweg herstel het is saam gegroepeer (DHR1) en diegene wat sekondêre skade ontwikkel het is saam gegroepeer (DHR2). CK aktiwiteit in serum het hoogtepunte bereik op d1 in beide subgroepe (DHR1: 1512 ± 413 u.L-1, DHR2: 1434 ± 202 u.L-1) en weer op d4 in die DHR2 groep (1110 ± 184 u.L-1). 'n Soortgelyke IL-6 en IL-10 reaksie is onmiddellik na oefening (in al die proefpersone) waargeneem. Addisionele IL-6 is vrygestel in die DHR2 subgroep en het ’n hoogtepunt bereik na 4h (10.3 ± 4.2 pg.mL-1), terwyl IL-10 reeds teruggekeer het na rustende waardes. IL-1ra (23.6 ± 8.8 pg.mL-1), CD68+ (5%) en CD163+ (3%) monosiete was aansienlik hoër in die DHR2 subgroep. Neutrofieltelling na 2h (DHR1: 8.6 ± 0.8 x109cells.L-1, DHR2: 11.4 ± 1.8 x109cells.L-1) het verband (p <0,02) gehou met CK-aktiwiteit op d4. In vergelyking met die DHR1 en kontrole groep was die lokalisering van NFĸB p65 in PBMC selkerne na 2h effens minder in die DHR2 subgroep. STAT3- en MPO-vlakke in die spiere was aansienlik hoër in die DHR2 subgroep as in die DHR1 subgroep na 4h en op d2 onderskeidelik. Die spierherstel proses was eenders vir alle individue wat aan die oefening deelgeneem het; 'n toename in Pax7+ Satelietselle (SC) is waargeneem na 4h (0.06 ± 0.01 Pax+ SC/spiervesel) en op d1 (0.07 ± 0.02 Pax+ SC/spiervesel). Gevolgtrekking: Gesonde jong mans kan verdeel word in diegene met 'n bevoegde en diegene met 'n minder doeltreffende vermoë om oefenings-geïnduseerde spierskade en die inflammatoriese reaksie te beheer. Die sitokien-reaksie, veral IL-6, blyk om 'n belangrike rolspeler in die ontwikkeling van sekondêre skeletspierskade te wees.
48
Henriksen, Peter Andrew. "Endothelial injury in atherosclerosis : identification of mediators and attenuation of inflammation by adenoviral augmentation of elafin and SLPI". Thesis, University of Edinburgh, 2005. http://hdl.handle.net/1842/29153.
Resumo:
Gene expression profiling failed to identify candidate ‘endothelial protective’ mediators and attention focussed on elafin and secretory leucocyte protease inhibitor (SLPI), two low molecular weight elastase inhibitors. Elafin has been demonstrated within human coronary arteries although its function as a locally active antiprotease, antagonising the inflammatory effects of human neurophil elastase (HNE) and bacterial injury has best been characterised within the lung. Here we have used adenovirus as a vector to deliver elafin and SLPI genes to human endothelial cells and macrophages. We have devised a protocol involving pre-complexing of adenovirus with lipofectamine to enhance gene delivery and subsequent gene expression in human endothelial cells and to facilitate gene delivery to human macrophages. Elafin and SLPI overexpression were associated with reduced inflammatory cytokine production in endothelial cells and macrophages in response to a range of atherogenic stimuli including oxidised LDL. This anti-inflammatory activity was associated with reduced activation of the transcription factor NF-κB and preservation of its inhibitory sub-unit IκBα. Furthermore, elafin overexpression protected endothelial cells from HNE mediated injury and attenuated HNE mediated impairment of macrophage apoptotic cell recognition. In summary, angiopoietin-2 was identified as a novel mediator produced by endothelial cells in response to oxidised LDL and may contribute to plaque development through facilitation of neointimal angiogenesis. Adenoviral overexpression of elafin and SLPI exhibited therapeutic potential through reducing inflammatory responses and protecting the structure and function of endothelial cells and macrophages in the presence of atherogenic stimuli.
49
Guo, Yancai. "Role of mast cell-derived mediators for leukocyte/endothelium-interactions and microvascular mechanisms in inflammation and in anaphylaxis /". Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-457-7.
50
Norppa, A. (Anna). "Association between periodontal and systemic inflammation:a study of pro- and anti-inflammatory mediators". Doctoral thesis, Oulun yliopisto, 2012. http://urn.fi/urn:isbn:9789514299681.
Resumo:
Abstract The principal aim of this study was to explore associations between systemic inflammatory status and periodontal inflammation and tissue destruction. The study population consisted of 61 patients with chronic periodontitis, 30 periodontally healthy control subjects, and 80 subjects with type 1 diabetes mellitus (T1DM). The T1DM subjects were periodontally treated and re-examined eight weeks after completion of the treatment. The periodontal measures included plaque, probing depth (PD), bleeding on probing (BOP) and attachment level (AL). The serum levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α, and interleukin (IL)-10, as well as the gingival crevicular fluid (GCF) level of matrix metalloproteinase (MMP)-8 were analyzed using commercially available ELISA assays, and serum high density lipoprotein (HDL) level using direct enzymatic methods. Serum IL-6 level associated significantly with the extent of inflamed periodontal pockets in T1DM subjects. Moreover, serum IL-6 modulated local periodontal inflammation in T1DM patients; periodontal healing turned out to be poorer in subjects with a high level of serum IL-6 than in those with a low level. Serum TNF-α/IL-10 ratio was three times higher in chronic periodontitis patients than in periodontally healthy control subjects. In T1DM subjects a significant inverse association between serum HDL level and the extent of inflamed periodontal pockets was found; subjects with a low serum HDL level presented 50% more inflamed periodontal sites than subjects with a high serum HDL level. A significant association between GCF MMP-8 level in shallow crevices and the extent of periodontal attachment loss in chronic periodontitis patients was observed. In conclusion, we focused on analyzing associations between systemic inflammatory status and periodontal conditions. According to our results, periodontal inflammation/infection is associated with systemic inflammatory status using serum IL-6, TNF-α/IL-10 ratio and HDL as indicators. Also, a high level of MMP-8 in GCF in shallow crevices could be indicative of higher susceptibility to periodontal infection and tissue destructionTiivistelmä Tutkimuksen tavoitteena oli tarkastella hampaiden kiinnityskudosten tulehduksen (pardodontiitti) ja siihen liittyvän inflammaation yhteyttä systeemiseen tulehdustilaan. Tutkimusaineistoon kuului 61 yleistervettä potilasta, joilla oli kohtalaisesti tai pitkälle edennyt parodontiitti, 30 yleistervettä yksilöä, joiden hampaiden kiinnityskudokset olivat terveet/lähes terveet (kontrolliryhmä), sekä 80 tyypin 1 diabetes mellitus (T1DM) potilasta, joilla esiintyi vaihtelevasti parodontiittia. T1DM potilaiden parodontiitti hoidettiin, ja heidät tutkittiin uudelleen kahdeksan viikon kuluttua hoidon päättymisestä. Tutkittavilta tarkastettiin plakin määrä, ientaskujen syvyys, ienverenvuoto ja hampaiden kiinnityskudoksen menetys. Systeemistä tulehdustilaa mitattiin käyttäen seerumin interleukiini (IL)-6, tuumorinekroosifaktori (TNF)-α ja interleukiini (IL)-10 tasoja. Lisäksi määritettiin ientaskunesteen matriksimetalloproteinaasi (MMP)-8 taso. Kaikki edellä mainitut tulehduksen välittäjäainetasot määritettiin käyttäen ELISA-menetelmää. T1DM potilaiden seerumin IL-6 pitoisuuden ja tulehtuneiden ientaskujen määrän välillä vallitsi positiivinen yhteys. Lisäksi havaittiin, että seerumin korkea IL-6 taso heikensi parodontiitin paranemista. T1DM potilailla havaittiin käänteinen yhteys seerumin HDL-pitoisuuden ja tulehtuneiden ientaskujen määrän välillä. Tutkittavilla, joilla seerumin HDL-taso oli matala (<1.35 mmol/l), oli 50 % enemmän tulehtuneita ientaskuja kuin niillä, joilla HDL-taso oli korkea (≥1.35). Parodontiitti-ryhmässä seerumin TNF-α/IL-10 suhde oli kolminkertainen verrattuna kontrolliryhmän vastaavaan ilmentäen voimakkaampaa matala-asteista tulehdusta parodontiitti-potilailla. Matalista (<4 mm) ientaskuista kerätyn ientasunesteen MMP-8 pitoisuuden ja parodontiitin vaikeusasteen välillä vallitsi merkittävä postiivinen yhteys parodontiitti-potilailla. Yhteenvetona, systeemisen tulehdustilan ja hampaiden kiinnityskudosten välillä vallitsee kaksisuuntainen yhteys; toisaalta parodontiitti lisää matala-asteista systeemistä tulehdustilaa ja toisaalta kohonnut systeeminen tulehdustila lisää alttiutta parodontiittiin ja siihen liittyvään inflammaatioon. Lisäksi ientaskunesteen korkea MMP-8 pitoisuus matalissa ientaskuissa voi merkitä lisääntynyttä alttiutta parodontiumin alueen tulehdukselle ja kudostuholle