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Webb, Ginette Rachel. "Cytokines and cytokine receptors in osteoarthritis." Thesis, University of Bristol, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.388158.
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Deller, Marc Christian. "Structural studies of cytokines and cytokine receptors." Thesis, University of Cambridge, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326028.
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Palmblad, Karin. "Cytokines and cytokine-directed intervention in experimental arthritis /." Stockholm, 2001. http://diss.kib.ki.se/2001/91-628-4589-6/.
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Affò, Silvia. "Cytokines and Cytokine-Receptors in the Pathogenesis of Alcoholic Hepatitis." Doctoral thesis, Universitat de Barcelona, 2014. http://hdl.handle.net/10803/145435.
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By performing a translational study we identified a specific pattern of genes differentially regulated in patients with severe alcoholic hepatitis (AH). A functional analysis of the gene expression profile showed several pathways deregulated in AH, including cytokines- cytokine receptor interaction. Within cytokine-cytokine receptor interaction pathway, Fn14 has been identified as the only receptor belonging to TNF superfamily to be exclusively up-regulated in patients with AH, and its expression has been shown to be associated with severity of the disease and mortality. We observed that Fn14 is upregulated in experimental models of progenitor cell expansion and co-expressed with Ep-CAM in livers of patients with AH, suggesting that Fn14 may regulate ductular reaction expansion. Moreover, we showed that Fn14 hepatic expression is regulated by ethanol and pro-fibrogenic factors, suggesting that alcohol abuse together with fibrogenic mediators may be directly responsible for the induction of Fn14 expression in ALD.
Furthermore, transcriptome analysis identified CCL20 as the most up-regulated cytokine in the liver of patients with AH. Hepatic expression and serum levels of CCL20 have been found elevated in patients with AH and have been showed to be associated with key clinical features of the disease such as fibrosis, endotoxemia and short-term mortality. These data suggest that besides playing a role in AH pathogenesis, CCL20 may also be considered as a potential non-invasive biomarker. We found that CCL20 hepatic expression is up-regulated in acute, chronic and acute-on chronic experimental model of liver injury induced by carbon tetrachloride (CCl4) and lipopolysaccharide (LPS) and their combination, respectively. Macrophages and hepatic stellate cells have been identified as the main CCL20 producing cell types in experimental models of acute-on-chronic liver injury. Moreover, we have showed that CCL20 exerts pro-fibrogenic and pro-inflammatory and effects on primary human hepatic stellate cells and on macrophages, suggesting that CCL20 may participate in both hepatic fibrosis and inflammation
during liver disease in an autocrine and paracrine manner. Finally, we have found that CCL20 mediates LPS-induced liver injury by promoting hepatocellular apoptosis, expression of pro-inflammatory and pro-fibrogenic mediators and by enhancing macrophages and neutrophils infiltrate recruitment.
In conclusion, during this thesis we performed two studies leading to the identification of new potential targets for therapy in AH. The identification of Fn14 and CCL20 as new potential targets for therapy in AH and their correlations with key hallmarks of the disease such as ethanol consumption, fibrosis, progenitor cells expansion and endotoxemia underline the complexity of this disease and the crosstalk between many mediators that occurs in AH.
The data presented in this thesis suggest that cytokines and cytokine-receptor pathway could represent a new potential target for therapy in ALD; and also provide new important insights and a useful resource for the study of the pathogenesis of this disease.El consumo de alcohol es una de las causas más importantes de mortalidad que pueden prevenirse en nuestro país. La hepatitis alcohólica (HA) se caracteriza por un proceso de inflamación hepática (fundamentalmente por infiltración de células polimorfonucleares), esteatosis masiva hepática, fibrosis pericelular y daño hepatocelular. En la actualidad no existen tratamientos efectivos para el tratamiento de la HA y por esta razón, existe una clara necesidad de identificar nuevas dianas terapéuticas para tratar a estos pacientes en los diferentes estadios de la enfermedad (esteatosis, inflamación y/o fibrogénesis). El objetivo principal de esta tesis fue investigar nuevas dianas terapéuticas para el tratamiento de la HA. Para alcanzar dicho objetivo, realizamos estudios traslacionales que permitieran identificar marcadores biológicos alterados en muestras humanas procedentes de hígados de pacientes con HA para estudiar la función que tienen en el desarrollo de la enfermedad in vitro e in vivo en modelos animales de diferentes tipos de daño hepático y valorar si podrían considerarse como dianas terapéuticas. Mediante la performación de nuestros estudios, identificamos a la vía de citoquinas-receptores de citoquinas como una de las vías con el mayor número de genes diferentemente regulados en pacientes con HA con respecto a controles sanos. Estudios en muestras humanas y en modelos animales de daño hepático nos permitieron identificar al receptor de citoquinas Fn14 y a la citoquina CCL20 como importantes mediadores de la HA, correlacionados tanto con aspectos clínicos característicos así como con la gravedad de la enfermedad. La vía de citoquinas y receptores de citoquinas y, de manera específica Fn14 y CCL20 han sido identificados como novedosos mediadores implicados en la patogénesis de la HA y por lo tanto como potenciales dianas terapéuticas. Por lo tanto, gracias a la identificación de un patrón de los genes diferentemente regulados en la HA, nuestros datos proporcionan importantes resultados novedosos para el estudio de la patogénesis de la HA.
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Ozaki, Akihiko. "Expression of cytokines and cytokine receptors in human Schwann cells." Kyoto University, 2008. http://hdl.handle.net/2433/135921.
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LU, ZHAO-YANG. "Cytokines et antagonistes de cytokines dans le myelome multiple." Nantes, 1993. http://www.theses.fr/1993NANT2079.
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Notre equipe a montre que l'interleukine-6 (il-6) est un facteur essentiel pour la croissance des cellules plasmocytaires malignes et que des traitements par anticorps anti-il-6 reduisaient croissance tumorale chez 50% des malades. La premiere partie de notre travail a consiste a rechercher les raisons pouvant expliquer une non-reponse au traitement. Nous avons ainsi developpe une methodologie nouvelle permettant de quantifier la production journaliere d'il-6 dans tout l'organisme. Nous avons montre que la production d'il-6 chez les malades non repondeurs etait trop forte, superieure au moins a 70 mg/jour, pour pouvoir etre inhibee par l'anticorps anti-il-6. Dans la deuxieme partie de notre travail, nous montrons que les 4 cytokines utilisant la meme chaine transductrice que l'il-6 sont egalement des facteurs de croissance plasmablastique (cntf, lif, il-11, osm). De plus, nous montrons que l'il-10, une nouvelle cytokine jouant un role important dans la differenciation lymphocytaire b normale, est egalement un puissant facteur de croissance des plasmocytes tumoraux. Ces resultats invitent a preciser rapidement le role eventuel joue par ces cytokines dans l'emergence du myelome multiple in vivo. Enfin, nous avons recherche des proteines pouvant bloquer la proliferation des cellules tumorales. Nous montrons que l'ifn-9 est un puissant inhibiteur en bloquant entre autre l'expression des recepteurs de l'il-6. L'antagoniste du recepteur de l'il-1 (il-ira) est un autre inhibiteur interessant capable de bloquer l'activation de l'environnement tumoral a produire de l'il-6. Cette activation est mediee par les pge-2 induites par l'il-1. En conclusion, l'etude des cytokines dans le myelome multiple permet de comprendre certains des mecanismes oncogeniques impliques dans cette pathologie et d'envisager des applications therapeutiques immediates de ces concepts
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Croxford, J. Ludovic. "Gene therapy for experimental allergic encephalomyelitis by delivery of inhibitory cytokines or cytokine inhibitors." Thesis, University College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.314201.
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Ulfgren, Ann-Kristin. "Cytokines in rheumatoid arthritis /." Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-3823-7/.
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Benrick, Anna. "Cytokines in metabolic functions /." Göteborg : Section of Endocrinology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, 2008. http://hdl.handle.net/2077/9608.
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Gilmore, William Hans. "Canine pro-inflammatory cytokines." Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.263791.
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Baudry, Nathalie. "Cytokines, hypoxie et microcirculation." Paris 5, 1995. http://www.theses.fr/1995PA05CD06.
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Le sepsis constitue une des complications les plus graves pouvant survenir dans le domaine de la réanimation ou dans le traitement des malades immunodéprimés. Il se caractérise par l'apparition de nombreuses complications, tel que l'hypotension associé à une diminution des résistances vasculaires périphériques et le syndrome de défaillance respiratoire (SDRA) responsable une hypoxie systémique. Le but de ce travail est d'étudier d'une part les effets des médiateurs du sepsis (" tumor necrosis factor ", interleukines 1 et 6) sur le tonus et la réactivité à la norépinéphrine (NE) du réseau artériolaire et d'autre part les effets de l'hypoxie systémique sur l'adhérence des leucocytes au niveau du réseau veinulaire. Ces travaux sont effectués sur un modèle expérimental original permettant l'étude in vivo de la microcirculation du muscle crémaster chez le rat anesthésié. Dans la première partie de ce travail, nous avions montré que le TNF, l'IL-1 et l'IL-6 ont des effets différents sur le réseau artériolaire du muscle crémaster de rat. L'administration de TNF entraîne une vasodilatation rapide des artérioles. Ces cytokines ont aussi des effets différents sur la réactivité des artérioles à la NE. Une hyporéactivité à la NE apparaît 2heures d'exposition en présence de TNF. Par contre, l'IL-1 induit une hyporéactivité à la NE dans les minutes qui suivent son administration sur la préparation à la NE dans les minutes qui suivent son administration sur la préparation. Aucune modification de réactivé à la NE n'est observée en présence d'IL-6. Dans la deuxième partie de ce travail, nous avons montré que l'hypoxie systémique augmente l'adhérence des leucocytes sur l'endothélium veinulaire du muscle crémaster de rat. Cet effet rapide de l'hypoxie systémique se produit même lorsque la préparation musculaire est suffisamment oxygénée. Cette observation peut expliquer la dissémination de la réponse inflammatoire au niveau des tissus périphériques lors du SDRA.
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Ghorayeb, Christine. "The regulation of human B cell effector cytokine profiles by exogenous T helper cell cytokines /." Thesis, McGill University, 2009. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111556.
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The Bar-Or laboratory recently reported that human B cells from normal subjects can produce either pro-inflammatory (TNF-alpha; LT) or regulatory (IL-10) effector cytokines depending on their context of activation. It was of interest to investigate the change in B cell cytokine profiles from normal subjects when activated in the context of a Th1 pro-inflammatory environment or a Th2 anti-inflammatory environment. It was found that the B cell regulatory network of effector cytokines from normal subjects is significantly modulated depending on the local cytokine milieu. In addition, it was of interest to study how MS patients' B cell cytokine network would respond in a Th1 pro-inflammatory and a Th2 anti-inflammatory context. It was found that MS patients' B cell cytokine network was dysregulated compared to B cell responses from normal subjects. The findings define a novel regulatory network involving human B cells from normal subjects and point to a newly discovered abnormality in MS patients' B cells.
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Shimokata, Kaoru. "Cytokines and Local Cellular Immunity." 名古屋大学医学部, 1997. http://hdl.handle.net/2237/6185.
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Hill, Andrew Graham. "Metabolic effects of proinflammatory cytokines." Thesis, University of Auckland, 1994. http://hdl.handle.net/2292/5522.
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The metabolic responses to trauma are well characterized and there is growing evidence supporting an important role for cytokines in its pathogenesis. Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Tumour necrosis factor (TNF) are synthesized in the brain, and other tissues, in trauma. In order to test the hypothesis that these cytokines play an important role in the metabolic responses associated with trauma, the effects of chronic cerebroventricular and peripheral infusions of IL-1, IL-6, and TNF on protein metabolism, weight loss, anorexia, and pyrexia in Sprague-Dawley rats were examined. Specifically the aims of these investigations were: 1. To examine the effect of chronic central nervous system exposure to the proinflammatory cytokines IL-1, IL-6, and TNF. 2. To investigate the role of anorexia in the catabolic responses to centrally infused IL-1. 3. To investigate the effects of IL-1 on the hypothalamic-pituitary-adrenal axis. 4. To investigate the role of glucocorticoids in the metabolic effects produced by chronic central infusion of IL-1. 5. To examine the metabolic effects of increasing doses of chronic peripherally infused IL-1 and to distinguish between those responses mediated centrally and those mediated outside the blood-brain-barrier. The major findings of these studies were: 1. IL-1, but not IL-6 in the same dose, nor TNF in a lower dose, produced net protein catabolism, weight loss, and pyrexia in excess of that produced by anorexia alone. 2. Furthermore the loss of weight and nitrogen did not require sustained elevations of glucocorticoids, as IL-1 infusion in corticosterone-replaced, adrenalectomized rats resulted in similar losses of weight and nitrogen as observed in sham-adrenalectomized animals infused with IL-1. 3. Peripheral infusion of increasing doses of IL-1 mimicked the effects of increasing injury with low doses causing a mild acute phase response (as assessed by a fall in serum iron and albumin and a leucocytosis) and larger doses causing net protein catabolism and weight loss. An attempt was made to distinguish between the central and peripherally mediated metabolic effects of IL-1 using a novel model utilizing peripheral infusions of IL-1 and central infusions of IL-1 receptor antagonist. Using this model the data were consistent with the hypotheses that pyrexia is mediated inside and outside the blood-brain barrier and that leucocytosis is mediated by a direct peripheral effect, probably on the bone-marrow. In conclusion, centrally produced IL-1 may play an important role in the metabolic responses associated with trauma and this is in excess of the anorexia and adrenocortical activation produced by centrally acting IL-1. Peripherally produced IL-1 may play a role in various organs such as the bone-marrow and the liver to produce other features of the metabolic responses associated with injury.
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Wang, Ling Jia. "Cytokines and the human ovary." Title page, contents and abstract only, 1992. http://web4.library.adelaide.edu.au/theses/09PH/09phw2458.pdf.
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Bibliography: leaves 151-179. Examines aspects of the distribution of leukocyte subpopulation in human corpus luteum, cytokine determination in human preovulatory follicular fluid, as well as the effects of cytokines on human granulosalutein cells; with the aim of investigating one of the ovarian regulatory systems, which may be controlled by immune cell-derived cytokines.
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Galligan, Carole Lynn. "Inflammatory cytokines in bovine mastitis." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/NQ47391.pdf.
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Zhang, Yan. "Cytokines and skeletal muscle wasting." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1999. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp03/MQ47124.pdf.
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Bemelmans, Marcus Henricus Adrianus. "Inflammatory cytokines in obstructive jaundice." Maastricht : Maastricht : Universitaire Pers Maastricht ; University Library, Maastricht University [Host], 1994. http://arno.unimaas.nl/show.cgi?fid=6812.
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Dennison, Jeremy M. T. J. "Cytoadhesion, cytokines and cerebral malaria." Thesis, University of Liverpool, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.337149.
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Parry, Robin Geoffrey. "Cytokines in minimal change nephropathy." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.341511.
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Reuter, Simone. "Étude de l’effet de la cytokine TNFa sur la régulation de l’expression de la ?-glutamyl-transférase humaine." Thesis, Nancy 1, 2008. http://www.theses.fr/2008NAN10054/document.
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La??-glutamyltransférase (GGT) est une enzyme membranaire qui catalyse l’hydrolyse du glutathion, le principal antioxydant cellulaire. Cette enzyme est surexprimée dans de nombreux cancers (p.ex. leucémies) et appartient à une famille multigénique d’au moins treize gènes. Le gène I, qui code pour la protéine active, est exprimé en trois ARNm (A, B et C), montrant tous la même phase de lecture ouverte mais différant dans leur région 5’ non traduite. A côté de l’implication de la GGT dans le développement des cancers, elle intervient également dans l’acquisition des résistances aux traitements anticancéreux et dans la synthèse des leukotriènes. Au cours de cette thèse, nous nous sommes intéressés aux mécanismes transcriptionnels qui régulent l’expression du gène I de la GGT. Plus particulièrement, nous avons étudié la régulation de la GGT après traitement des cellules K562 avec l’ester de phorbol, TPA, et la cytokine pro-inflammatoire, TNF?? Ces deux substances activent les facteurs de transcription AP-1 et NF-?B, qui sont connus pour réguler des gènes impliqués dans le développement des chimiorésistances. Nos résultats montrent que les deux promoteurs B et C de la GGT ainsi que les trois ARNm A, B et C, la protéine GGT ainsi que l’activité enzymatique de la GGT sont induits par le TNF?, mais pas par le TPA, dans la lignée cellulaire K562, qui est établie à partir de cellules issues d’une leucémie myéloïde chronique. Vu que l’induction du promoteur C de la GGT par le TNF? est fortement diminuée avec la curcumine, un agent chimiopréventif utilisé comme inhibiteur de la voie de signalisation NF-?B, nous avons émis une première hypothèse selon laquelle le facteur de transcription NF-?B serait impliqué dans la régulation du promoteur C de la GGT dans les cellules K562. Afin de prouver notre hypothèse nous avons utilisé des siRNA ciblant spécifiquement les deux sous-unités les plus représentées de NF-?B, p50 et p65, et effectivement l’induction du promoteur C de la GGT par le TNF? est inhibée par ces siRNA. Des expériences par co-transfection avec des protéines de la voie NF-?B, TRAF2, TRADD, I?B? et p65, confirment davantage cette hypothèse selon laquelle le promoteur C de la GGT est régulé par la voie de signalisation NF-?B dans les cellules K562. Des expériences par mutation ont ensuite permis d’identifier le site sur l’ADN qui est responsable de l’induction du promoteur C de la GGT par le TNF? dans les cellules K562. Ce site, localisé de -111 à -123 par rapport au site d’initiation de la transcription, est au moins capable de fixer le facteur de transcription p50 NF-?B. A proximité de ce site, nous avons identifié un autre site fonctionnel, localisé de - 73 à – 92 par rapport au site d’initiation de la transcription, qui lie le facteur de transcription Sp1. Des analyses par chromatine immunoprécipitation (ou ChIP) ont confirmé la liaison des facteurs de transcription NF-?B et Sp1 sur le promoteur C de la GGT et montrent de plus que l’ARN polymérase II est également recruté à cet endroit précis du promoteur. En outre, ces analyses montrent que le traitement au TNF? induit la liaison des facteurs de transcription p50 NF-?B et Sp1, comparé par rapport aux cellules non traitées, sur le promoteur, et augmente considérablement le recrutement de l’ARN polymérase II à cet endroit précis du promoteur C de la GGT, expliquant ainsi l’induction observée du promoteur C de la GGT après traitement au TNF?. En conclusion, l’induction de la GGT par le TNF? peut avoir plusieurs significations biologiques importantes, à savoir augmenter la résistance aux médicaments anticancéreux, se défendre contre un stress oxydant, ou induire la synthèse des leukotriènes et donc médier l'inflammation?-glutamyltransferase (GGT) is an enzyme that catalyzes the hydrolysis of glutathione, the major cellular antioxidant. This enzyme is overexpressed in many cancers (for example in leukemia) and belongs to a multigene family of at least thirteen genes. The GGT gene I, which encodes the active protein, is transcribed into three mRNAs (A, B and C), all showing the same open reading frame but diffeiring in their 5' untranslated region. Besides the involvement of GGT in the development of cancers, it is also involved in the acquisition of resistance to anticancer treatments and in the synthesis of leukotrienes. During this thesis, we were interested in the transcriptional mechanisms that regulate GGT gene I expression. Specifically, we studied the regulation of GGT after treatment of K562 cells with the tumor promoter TPA, and the pro-inflammatory cytokine, TNFa. Both substances activate the transcription factors AP-1 and NF-?B, which are known to regulate genes involved in the development of chemoresistance. Our results show that the two GGT promoters B and C and the three mRNA A, B and C, as well as GGT protein and GGT enzymatic activity are induced by TNFa, but not by TPA in K562 cells, which are originated from a chronic myeloid leukemia. Since the induction of the GGT promoter C by TNFa is reduced with curcumin, a natural chemopreventif agent used as an inhibitor of the NF-?B signaling pathway, we supposed that the transcription factor NF-?B is involved in the regulation of the GGT promoter C in K562 cells. To prove our hypothesis, we used siRNA targeting specifically the two main subunits of NF-?B, p50 and p65, and indeed the induction of the GGT promoter C by TNFa is inhibited by these siRNA. Co-transfection assays with proteins of the NF-?B signaling pathway, TRAF2, TRADD, I?Ba and p65, further confirm our hypothesis that the GGT promoter C is regulated via the NF-?B signaling pathway in K562 cells . Mutation experiments then identified the site on the DNA that is responsible for the induction of the GGT promoter C by TNFa in K562 cells. This site, located at -123 to -111 base pairs compared to the transcriptional start site, is able to bind at least the transcription factor p50 NF-?B. Near this site, we have identified another functional site, localized at - 73 - 92 base pairs compared to the transcriptional start site, which binds the transcription factor Sp1. Analysis by chromatin immunoprecipitation (or ChIP) confirmed the binding of the transcription factors NF-?B and Sp1 on the GGT promoter C and show that RNA polymerase II is also recruited at this specific location of the GGT promoter C. In addition, the analysis showed that treatment with TNFa induced binding of the transcription factors p50 NF-?B and Sp1, compared to untreated cells, and strongly increases the recruitment of RNA polymerase II to this location of the GGT promoter C, thus explaining the observed induction of the GGT promoter C after treatment with TNFa. In conclusion, the induction of GGT by TNFa may have several important biological significance, namely to increase resistance to anticancer drugs, to defend against oxidative stress or to induce leukotriene synthesis and thus to mediate inflammation
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Derouet, Damien. "Activation des récepteurs de cytokines de la famille de l'interleukine-6." Thesis, Angers, 2018. http://www.theses.fr/2018ANGE0006.
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Les cytokines de la famille de l’IL-6 possèdent comme caractéristique commune la capacité à recruter une chaine réceptrice membranaire nommée gp130. Au début de notre étude, cette famille comptait 8 membres : IL-6 et son homologue viral (vIL-6), IL-11, LIF, OSM, CNTF, CT-1 et CLC. Depuis, cette famille s’est enrichie de trois nouveaux membres, NP, IL-27 et IL-31. Ces cytokines sont essentielles au développement (LIF et CT-1) ou sont impliquées dans l’hématopoïèse, les réponses immunitaires et l’inflammation (IL-6, IL-11, IL-27, IL-31 et OSM) alors que d’autres agissent plus particulièrement au niveau du système nerveux, comme NP, CLC et CNTF. Le premier axe de recherche de ma thèse a porté sur l’identification d’un nouveau membre de cette famille,la neuropoïétine (NP), et plus précisément sur la caractérisation de son profil d’expression tissulaire et l’identification de son récepteur, des principales voies de signalisation intracellulaire induites ainsi que ses fonctions biologiques. Le deuxième axe de recherche a consisté à étudier la capacité de CLC à se comporter comme un ligand alternatif du récepteur tripartite au CNTF, impliqué dans le développement neuronal. Pour cela, nous avons mis en évidence la présence de la cytokine CLC et de ses partenaires de sécrétion, dans l’environnement des motoneurones lors du développement embryonnaire chez la souris. Enfin, le dernier axe de recherche s’est focalisé sur le rôle des états de glycosylation de CLC sur la sécrétion des cytokines composites CLC/CLF et CLC/solCNTFRαMembers of the interleukin 6 (IL-6) cytokine family share a common characteristic, the capacity to signal via thegp130 subunit receptor. This family contains 8 members : IL-6 and its viral counterpart (vIL-6), IL-11, LIF, OSM, CNTF, CT-1 and CLC. This family has been more recently enriched with three new members, neuropoietin (NP), IL-27 and IL-31. These proteins are involved in development (LIF and CT-1), in hematopoiesis, immune responses and inflammation, such as IL-6, IL -11, IL-27, IL-31 and OSMor act in the nervous system (NP, CLC and CNTF). My first research work was focused on the identification of a new member of this family, neuropoietin. More specifically, this study allowed determining its tissue expression profile, its complex receptor and the signaling pathways induced, and its biological functions. A second research project was focused on determining whether CLC may constitute an alternative ligand for the CNTF receptor, involved in the neuronal development. We have evidenced the presence of CLC and its secretory partners, in the environment of motoneurons during embryonic development in mice. Finally, I have evaluated the role of the glycosylationstates of CLC on the secretion of the composite cytokines CLC/CLF and CLC/solCNTFR
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Wong, Hei-kiu. "Functional roles of rarely-used synonymous codon and sequences variation in type I cytokine receptors." Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B42609999.
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Bonaccorso, Stefania. "Cytokines and depression: a neurochemical hypothesis." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2005. http://arno.unimaas.nl/show.cgi?fid=6039.
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Patrick, Guy M. "Studies of cytokines in alloimmune responses /." Title page, table of contents and abstract only, 1998. http://web4.library.adelaide.edu.au/theses/09PH/09php314.pdf.
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Flint, Melanie Sarah. "Induction and regulation of epidermal cytokines." Thesis, Imperial College London, 1999. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.322116.
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Goncalves, Mario Nuno Penha. "Equine interferon-gamma and associated cytokines." Thesis, University of Glasgow, 2000. http://theses.gla.ac.uk/1064/.
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Cytokines are small proteins or glycoproteins that mediate cellular growth and differentiation and regulate immune responses. Upon encounter with antigen, CD4+ T cells are able to influence the character of the immune response elicited through the expression of distinct types of cytokines. Thl cytokines, especially IFN-γ but also TNF-β and IL-2, constitute one such pattern of expression, promoting cell mediated immune responses. In a broader sense, interleukin-12 and interleukin-18 can also be classified as type I cytokines in as much as they are able to shift the CD4+ cytokine expression pattern to a Thl phenotype and specifically stimulate IFN-γ production not only by T helper cells, but also by cytotoxic T cells and natural killer cells. The purpose of the present project was to develop equine Thl cytokines, making them available for dissecting the equine immune system, particularly in what concerns to defence mechanisms against infectious micro-organisms. Following the trend in human medicine, the cytokines produced will be useful for the development of new therapeuticals and prophylactics to be used in the control and prevention of infectious diseases of the horse. For this effect we have initiated studies on equine interferon-gamma and related cytokines and obtained the following results. Equine interferon-gamma was cloned and produced in a variety of heterologous protein-expression systems. The biological activity of recombinant equine interferon-gamma was assessed in vitro. Polyclonal serum preparations against equine interferon-gamma, obtained by immunization with recombinant protein, were recovered and characterised. Also described is the cloning of the interferon-gamma inducing cytokines equine interleukin-12 and equine interleukin-18. The potential use of the cloned equine cytokine genes as vaccine adjuvants was evaluated by DNA co-administration with plasmids encoding the equine influenza virus antigens haemagglutinin and nucleoprotein, followed by viral challenge.
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McNerlan, Susan E. "Analysis of cytokines in synovial fluid." Thesis, Queen's University Belfast, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.333839.
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Van, Wely Catherine Ann. "Cytokines, lymphocyte surface molecules and homing." Thesis, University College London (University of London), 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.298867.
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VIGARIO, ANA MARGARIDA. "Cytokines et pathogenese du neuropaludisme murin." Paris 7, 2001. http://www.theses.fr/2001PA077119.
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Le paludisme reste la maladie tropicale la plus importante. Le neuroplaludisme et l'anemie severe sont les deux causes principales de la mort. Une meilleure comprehension des mecanismes impliques dans la pathogenese du paludisme, en particulier du neuropaludisme, est donc des plus important. Differentes etudes, principalement dans les modeles rongeurs, ont demontre l'importance des cytokines pro-inflammatoires dans la pathogenese du neuropaludisme. Nous avons etudie le role de l'ifn- dans le developpement des signes neurologiques a l'aide de souris deficientes pour la chaine du recepteur de l'ifn- infectees par plasmodium berghei anka (modele pour le neuropaludisme). Ces souris deficientes sont resistantes au neuropaludisme, confirmant un role pour l'ifn- dans la pathogenese de cette maladie. Nous avons observe de plus, une diminution du nombre de leukocytes sequestres dans le capillaires cerebraux des les souris deficientes par rapport aux souris sauvages. Ce resultats nous a conduit a etudier ce phenomene dans des differents couples hotes/parasites presentant differente susceptibilite pour le neuropaludisme. Nous avons demontre que les cellules t cd8 sequestres dans les capillaires cerebraux sont responsables des signes neurologiques et de la mort qui s'ensuit. L'effet d'une autre cytokine, l'ifn-, sur le developpement du neuropaludisme a aussi ete analyse. Les souris infectees et traitees par cette cytokine sont proteges contre le neuropaludisme, mais meurent plus tard. L'effet de cette cytokine dans des souris infectees par plasmodium yoelii (modele pour l'anemie severe) a ete aussi analyse. Nous avons montre que le traitement par l'ifn- inhibe la parasitemie pour des souches de parasites qui ont un tropisme pour les reticulocytes, en bloquant la reticulocytemie induite par l'infection.
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Simpson, Kenneth J. "Studies on cytokines in liver pathophysiology." Thesis, University of Edinburgh, 1997. http://hdl.handle.net/1842/21531.
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Aims of the thesis: To study the mechanisms of chemokine production that may occur during hepatic disease, the role of chemokines in hepatic injury and repair following paracetamol poisoning and hepatic expression of chemokines in patients with liver disease. In addition, the roles of tumour necrosis factor alpha (TNF) and stem cell factor (SCF) were also studied following paracetamol poisoning. Results: Both CXC and CC chemokines were produced during monocyte adhesion with human hepatoma cell lines. IL-8 production was dependent on proinflammatory cytokine production. In contrast, CC chemokine production appeared to be dependent on free radical activation of NF-κB. Direct TNF stimulated IL-8 production was mediated by TNF RI receptors via a protein kinase C pathway and was inhibited by dexamethasone. Both CXC and CC chemokines were detectable in human liver biopsies in patients with hepatitis C, hepatic allograft rejection and alcoholic hepatitis. Hepatic CXC and CC chemokines were also induced following paracetamol poisoning, inhibition of MIP2 and MIP1 alpha increased 3 day mortality and augmenting MIP2 expression was associated with accelerated hepatic regeneration. Hepatic TNF expression was not induced following paracetamol poisoning and inhibiting TNF was not associated with protection from hepatic injury. SCF was present within the liver at high concentration and located in both hepatocytes and bile ducts. Paracetamol poisoning was associated with reduced hepatic SCF concentrations and inhibiting SCF was associated with delayed hepatic regeneration. Conclusions: Both adhesion mediated and direct proinflammatory cytokine stimulation induce hepatic chemokine production. Chemokines are expressed in liver tissue from patients with hepatitis and therefore may be implicated in the pathogenesis of hepatic inflammation.
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Schirmer, Stephan Henrik. "Circulating cells and cytokines in arteriogenesis." [S.l. : Amsterdam : s.n.] ; Universiteit van Amsterdam [Host], 2008. http://dare.uva.nl/document/115099.
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Al, Turaiki Wael. "Regulatory immune cytokines in RSV infection." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2008039/.
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Antibody production in the lungs is an essential defence mechanism against respiratory pathogens. However, little is known about the local activation of B cells in the lung. The production of BAFF and APRIL by airway epithelial cells could contribute to local recruitment, activation, class switch recombination and antibody production by B cells in the lung. In vitro, BEAS-2B cells were used to characterize BAFF and APRIL production simulated either by RSV infection or addition of cytokines. RSV and IFN-β significantly induced expression of BAFF mRNA and protein but not APRIL. BAFF mRNA reached significantly high levels at 12h and declined at 48h after either RSV infection or IFN-β stimulation. Western blot analysis of resting epithelial cells showed that membrane BAFF was expressed by resting cells. On RSV infection or IFN-β stimulation, expression of membrane BAFF increased at 12 and 24hours and disappeared at 48h, which suggests soluble BAFF was cleaved from the membrane and released into the culture supernatant by 48h, where it was measured by ELISA. When BEAS-2B cells were infected with RSV after pre-incubation with anti-IFN β, expression of BAFF was blocked, which indicates that airway epithelial cells can produce BAFF in an interferon dependent manner. BEAS-2B cells did not express CXCL12, CXL13, CCL19 or CCL21, which indicates there are other potential sources that express these chemokines during RSV infection rather than the airway epithelium. A murine model of RSV infection was used to examine expression of BAFF, APRIL and of the chemokines CXCL12, CXCL13, CCL19 and CCL21. Cytokine mRNA and RSV N gene expression were measured by Taqman PCR in lung tissue from control mice at day 0 and mice challenged with RSV (A2 strain) or control UV-treated RSV at days 1, 2, 4, 7, 8, 10, 14 and 21 days after RSV infection by ELISA. RSV N RNA was significantly detected at day 1, 2 and 4 after RSV infection compared to UV RSV control. BAFF mRNA expression was increased significantly after RSV infection on day 1 ,7 and 8 in comparison to UV treated RSV control at the same time points. Equally, BAFF protein was also elevated significantly after RSV infection at days 1, 2, 4, 7 and 8 in comparison to UV- RSV control at the same time points. CXCL13 mRNA expression was increased significantly after RSV infection on day 1 and 7 in comparison to UV-RSV control at the same time points. Moreover, CXCL13 protein was increased significantly after RSV infection at day 1, 2 and 7 in comparison to UV RSV control at the same time points. CXCL12, CCL19 and CCL21 mRNA and protein levels were not increased significantly after RSV infection, which may indicate they are not active during RSV infection. Examination of mouse lung sections showed strong positive staining of B cells (CD20) following RSV infection at day 1, 2, 4, 7 and 8 and FACS analysis B cells numbers were increased significantly at day 6 and 8 following RSV infection relative to UV-RSV control. RSV infection results in up-regulated BAFF and CXCL13 expression, consistent with a role for CXCL13 in recruiting B cells and BAFF in promoting airway B cell survival or differentiation. Collectively, these results suggest that the airway epithelial could help recruit and support B cell growth and development and Ab production in the lung.
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Cebo, Christelle. "Activité lectinique des cytokines humaines : implications dans les voies de transduction lymphocytaires et modélisation de l'interaction cytokine-ligand." Lille 1, 2001. https://pepite-depot.univ-lille.fr/RESTREINT/Th_Num/2001/50376-2001-145.pdf.
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Chevalier, Anne Sophie. "Utilisation thérapeutique du G-CSF et du GM-CSF en hématologie." Paris 5, 1993. http://www.theses.fr/1993PA05P248.
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Aggad, Dina. "Diversité des interférons et de leurs récepteurs chez le Danio rerio." Montpellier 2, 2009. http://www.theses.fr/2009MON20117.
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Les IFNs sont un groupe de cytokines définis par leur activité antivirale. Chez les mammifères, ils sont divisés en trois groupes. Ils fixent tous des complexes récepteurs distincts et possèdent une structure génique différente. Les types I (principalement α et β) ont un seul exon, le type II (γ) quatre exons et le type III (λ) cinq. Les types I et III constituent un sous-groupe connu sous le nom « d'IFNs induits par les virus », car ils sont directement induits par une infection virale, alors que le type II ne l'est pas. La présence d'IFN induits par les virus et d'IFNγ (possédant 4 exons) ont été signalé dans toute les études poussées chez les poissons, la plupart, sinon tous, possèdent plusieurs gènes codant pour ces IFNs. La classification des IFNs induits par les virus chez les poissons est très controversée, nous avons pris parti de les nommer IFNφ (possédant 5 exons). Au cours de cette thèse nous avons identifié un IFN en plus appartenant aux IFNφs, nous avons caractérisé les propriétés des IFNφs et IFNγs et nous avons identifié leurs complexes récepteurs in vivo. Le génome du danio code pour 4 IFNφs et 2 IFNγs, nous avons montré que l'expression et le profil d'induction de ces IFNs sont différents, qu'ils possédaient une activité biologique antivirale et que les IFNφs étaient capables de protéger contre l'infection virale. Finalement l'utilisation d'expériences de perte et de gain de fonction, nous ont permis d'identifier les composants transmembranaires des complexes récepteursInterferons are a group of cytokines defined by their antiviral activities. In mammals, IFNs are divided into three groups according to their receptor usage. In addition to using distinct receptor complexes, the three mammalian types of IFN also have distinct genetic structure: type I (mainly α and β ) IFN genes have a single exon, type II (γ) IFNs have four exons, while type III (λ) IFNs have five. Type I and type III IFNs together constitute a distinct subgroup known as “virus-induced IFNs” as they are directly induced by viral infections while type II is not. Virus-induced fish IFNs and IFN γ (with 4 exons) have now been reported in all deeply studied fish species; most, if not all, teleost species possess several genes encoding these IFNs. The classification of fish virus-induced IFNs remains controversial, we took advantage of naming IFNφ (with 5 exons). In this work we identified a fourth IFN, which belongs to IFNφs, we characterized the properties of IFNφs and IFNγs and we have found their receptor complexes in vivo. The danio genome encodes 4 IFNφs and 2 IFNγs, we showed that the expression profile and induction of these IFNs are different, they possess antiviral biological activity and the IFNφs were able to protect against the viral infection. Using loss of function and gain of function analysis, we finally identified the transmembrane components of their receptor complexes
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Goulesque, Bruno. "Remodelage osseux et cytokines dans les lymphopathies malignes : corrélation entre paramètres histomorphométriques et dosage sérique des cytokines." Montpellier 1, 1992. http://www.theses.fr/1992MON11019.
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王熙喬 and Hei-kiu Wong. "Functional roles of rarely-used synonymous codon and sequences variation in type I cytokine receptors." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B42609999.
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Boukhedouni, Nesrine. "Mécanismes immunologiques impliqués dans la perte des mélanocytes au cours du vitiligo." Thesis, Bordeaux, 2018. http://www.theses.fr/2018BORD0300.
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Le vitiligo est une dermatose inflammatoire caractérisée par une perte progressive des mélanocytes de la lame basale de l’épiderme. Cette pathologie reste à ce jour orpheline de traitement efficace. Toutefois, les mécanismes qui sont liés à la perte des mélanocytes restent débattus et impliquent un détachement des mélanocytes de la lame basale ou leur mort cellulaire par apoptose. Nous avons montré au sein de notre équipe l’implication des lymphocytes T CD8+ effecteurs mémoires dans la pathogénie du vitiligo. Ces populations produisent des niveaux élevés de deux cytokines inflammatoires qui sont, le TNF-α (tumor necrosis factor) et l’IFN-γ (interféron γ), suggérant ainsi un rôle majeur de ces deux cytokines dans la pathogénie du vitiligo. L’objectif de mon projet de thèse est d’étudier les mécanismes immunologiques impliqués dans la perte du mélanocyte au cours du vitiligo. Ainsi, nous avons observé dans les zones péri-lésionnelles de vitiligo ou lésionnelles de psoriasis, une localisation suprabasale des mélanocytes et une anomalie de l’expression de la E-cadhérine dans l’épiderme, protéine majeure impliquée dans l’attachement des mélanocytes. Nous avons également montré l’absence de la mort cellulaire par apoptose des mélanocytes au niveau cutané chez les patients atteints de vitiligo et/ou de psoriasis. En se basant sur ces observations, nous nous sommes donc intéressés à évaluer les effets combinés du TNF-α et de l’IFN-γ sur l’adhésion des mélanocytes. Nos résultats ont montré que les deux cytokines combinés diminuent l’expression du gène codant la Ecadhérine et entrainent probablement la redistribution de cette protéine. De plus, nous avons observé que ces deux cytokines en combinaison altèrent l’expression de la E-cadhérine dans un modèle d’épidermes reconstruits pigmentés in vitro. Cette altération était associée à une augmentation des niveaux de la E-cadhérine soluble (sE-cad) au niveau des surnageants de culture. D’une manière intéressante, nous avons montré que ces deux cytokines induisent l’expression kératinocytaire de la métalloprotéase 9 (MMP9) dont l’action est connue pour cliver la E-cadhérine sous sa forme soluble, participant ainsi au détachement des mélanocytes. Des taux élevés de MMP9, mais également de la sE-cad sont retrouvés dans le sérum des patients atteints de vitiligo. L’inhibition de la MMP9 dans des modèles in vitro et in vivo empêche les effets combinés du TNF- α et de l’IFN-γ sur le détachement des mélanocytes permettant leur stabilisation à la lame basale. Par ailleurs, comme nous avons montré que la survie des mélanocytes n’était pas altérée dans le vitiligo, nous nous sommes intéressés à évaluer l’action combinée du TNF-α et de l’IFN-γ sur la fonction, le phénotype des mélanocytes et leur production des médiateurs inflammatoires. Nous avons montré que ces deux cytokines en combinaison inhibent l’expression des gènes mélanocytaires (MITF, TYR, DCT) et favorisent l’induction des chimiokines CXCL9 et CXCL10, de la cytokine inflammatoire TNF-α et de la molécule d’adhésion ICAM-1, suggérant un rôle majeur des mélanocytes dans la promotion de l’inflammation. Enfin, considérant que la voie de signalisation du récepteur de l’IFN-γ est dépendante de la voie JAK/STAT, nous avons étudié l’impact de l’inhibition de cette voie dans les effets induits dans nos modèles, et avons montré au niveau de l’expression des gènes, une amélioration des gènes associés à la fonction mélanocytaire et une inhibition de ceux associés à l’inflammation. L’ensemble de nos résultats mettent en évidence un nouveau mécanisme pour expliquer la perte des mélanocytes et identifie MMP9 ainsi que les inhibiteurs de JAK comme des cibles thérapeutiques prometteuses permettant ainsi de mieux comprendre les mécanismes physiopathologiques au cours du vitiligo et d’établir un lien direct entre immunité, facteurs solubles inflammatoires et perte des mélanocytes au cours du vitiligoVitiligo is a chronic inflammatory skin disorder characterized by a progressive loss of melanocytes. This stigmatizing disease has a major social impact and no real effective therapies have been reported so far. However, the mechanisms leading to melanocyte disappearance remain debated and include melanocyte detachment and/or death. The role of the immune response has now been well described, implying CD8+ effector memory T cells that produce high levels of inflammatory cytokines as TNF-α (tumor necrosis factor) and IFN-γ(interferon γ), suggesting the involvement of these two cytokines in the pathogenesis of vitiligo. Thus, the aim of this project is to study the interplay between the inflammatory response characterizing vitiligo disease and melanocyte loss. We first observed that melanocytes are located in suprabasal layers of the epidermis in perilesional skin of vitiligo and lesional skin of psoriasis patients, which was associated with an altered expression of E-cadherin, a major protein involved in melanocyte attachment to the basal membrane. Such suprabasal melanocytes did not undergo apoptosis. Based on these observations, we next investigated the combined effects of TNF-α and IFN-γ on melanocyte adhesion. We showed that these two cytokines decrease E cadherin gene expression and probably induce a redistribution of E-cadherin. In addition, these two cytokines in combination altered the expression of E-cadherin in reconstructed human pigmented epidermis in vitro. This finding was associated with increased levels of soluble E-cadherin in culture supernatants. Furthermore, TNF-α and IFN-γ induced the production of matrix metalloproteinase 9 (MMP9) by keratinocytes, leading to the cleavage of the E-cadherin. Inhibition of MMP9 prevents the combined effects of TNF-α and IFN-γ on melanocyte detachment and led to their stabilization to the basal membrane of epidermis in vitro and in vivo models. Since we demonstrated that melanocyte survival is not impaired in vitiligo, we assessed the impact of these two cytokines on melanocyte function, phenotype and inflammation. We demonstrate that the combination of TNF-α and IFN-γ inhibits the expression of genes involved in melanocyte function (MITF, TYR, DCT) and promote the induction of the chemokine ligands CXCL9 and CXCL10, the inflammatory cytokine TNF-α and adhesion molecule ICAM-1, suggesting an important role of melanocytes in the promotion of inflammation. Lastly, considering that the signaling pathway of IFN-γ involves activation of the JAK / STAT pathway, we studied the impact of the inhibition of that pathway in our models. Our results show that the JAK inhibition suppressed the effects of TNF-α and IFN-γ on melanocyte function, on the release of pro-inflammatory mediators and led to the melanocyte stabilization to the basal membrane of epidermis. All of our results highlight a new mechanism to explain the loss of melanocytes and identify MMP9 and JAKs as promising therapeutic targets to better understand the physiopathological mechanisms during vitiligo and establish a direct link between immunity, soluble factors. Inflammation and loss of melanocytes during vitiligo
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Dellacasagrande, Jérôme. "Infection de monocytes humains par Coxiella burnetii : modulation par cytokines." Aix-Marseille 2, 1999. http://theses.univ-amu.fr.lama.univ-amu.fr/1999AIX20672.pdf.
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Coxiella burnetii, l'agent pathogène responsable chez l'homme de la fièvre Q, est une bactérie intracellulaire stricte qui réside dans les monocytes/macrophages. Ces cellules sont douées de puissantes capacités microbicides qui leur confèrent un rôle essentiel dans la lutte anti-bactérienne. Ainsi, paradoxalement, C. Burnetii a pour cible les cellules destinées à la détruire. L'état d'activation des monocytes/macrophages, et par conséquent leur potentiel bactéricide, est contrôlé par les cytokines. Nous avons étudié l'effet des cytokines sur la survie de C. Burnetii dans les monocytes/macrophages humains. Nous avons identifié un déficit de bactéricidie des monocytes de patients atteints d'endocardite à C. Burnetii tandis que les monocytes de sujets sains éliminent rapidement la bactérie. Ce déficit n'est pas dû à un défaut général des fonctions microbicides des monocytes puisqu'il n'affecte que la réponse dirigée contre C. Bumetii. Il est lié à la surproduction de Tumor Necrosis Factor (TNF) par les monocytes des sujets atteints d'endocardite à C. Burnetii. Dans un modèle d'infection de monocytes de la lignée THP1, nous avons étudié les signaux nécessaires à la production de TNF. En réponse à C. Burnetii, l'ARN messager codant le TNF est détecté de façon précoce et transitoire. L'utilisation d'anticorps ou de peptides bloquant l'activité de l'intégrine αvβ3, le récepteur cellulaire de C. Burnetii, inhibe cette synthèse de TNF. Le lipopolysaccharide (LPS) bactérien stimule, lui, la production de TNF de la même manière que la bactérie. Notre hypothèse est que la production de TNF par les monocytes THP1 en réponse à C. Burnetii se déroule en deux étapes : la bactérie se fixe d'abord au monocyte via l'intégrine αvβ3, ce qui permet ensuite au LPS d'induire un fort signal de production de TNF. Le mode de vie intracellulaire à pH acide de C. Burnetii est vraisemblablement responsable de la faible efficacité de l'antibiothérapie dans le traitement de la fièvre Q chronique. L'activation des fonctions microbicides des monocytes/macrophages par les cytokines pourrait constituer un traitement complémentaire. L'interféron gamma (IFNγ) est connu pour être la principale cytokine activatrice des monocytes/macrophages. Dans le cas particulier de la fièvre Q, il a été montré que les lymphocytes· des malades présentent un déficit de production d'IFNγ en réponse à C. Burnetii. Nous avons évalué l'effet de l'IFNγ sur des monocytes THP1 préalablement infectés par C. Burnetii. L'IFNγ diminue la viabilité bactérienne et induit la mort par apoptose des cellules infectées. Le mécanisme. D'action de l'IFNγ est indépendant de la production des dérivés actifs de l'oxygène et de l'interleukine-1. Par contre, le TNF joue un rôle majeur dans l'apoptose induite par l'IFNγ. La mort par apoptose des cellules infectées par une bactérie intracellulaire stricte est probablement le·moyen le mieux approprié pour éliminer une telle bactérie. Enfin, nous avons montré que l'infection des monocytes par C. Burnetii diminue leur capacité de migration transendothéliale. Un tel résultat n'ayant jamais été décrit, les conséquences physiopathologiques qu'il implique restent à déterminer.
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Layé, Sophie. "Régulation des cytokines et de leurs récepteurs dans le système nerveux central sous l'effet d'une inflammation périphérique induite par le lipopolysaccharide." Bordeaux 2, 1995. http://www.theses.fr/1995BOR28395.
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Fisher, Linda. "Inflammatory cytokines and NFκB in Alzheimer’s disease." Doctoral thesis, Stockholm University, Department of Neurochemistry, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-990.
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Alzheimer’s disease is the most common form of dementia. It is a neurodegenerative disorder characterized by extracellular senile plaques and intracellular neurofibrillary tangles. The main constituent of the senile plaques is the neurotoxic β-amyloid peptide. Surrounding the senile plaques are activated astrocytes and microglia, believed to contribute to neurotoxicity through secretion of proinflammatory cytokines, like interleukin-1β and interleukin-6. For many inflammatory actions, including the cytokine induction in glial cells, the transcription factor NFκB plays a key role. This suggests that therapeutical strategies aimed to control the development of Alzheimer’s disease could include administration of drugs that hinder NFκB activation.
The major aim of this thesis was to examine the effects of β-amyloid together with interleukin-1β on cytokine expression as well as NFκB activation in glial cells. The possibility to block NFκB activation, and downstream effects like interleukin-6 expression, by using an NFκB decoy was investigated. The possibility to improve the cellular uptake of the decoy by linking it to a cell-penetrating peptide was also investigated.
The results obtained provide supportive evidence that inflammatory cytokines are induced by β-amyloid, and that they can indeed potentiate its effects. The results further demonstrate that by blocking NFκB activation, the induction of interleukin-6 expression can be inhibited. By using an improved cellular delivery system, the uptake of the NFκB decoy and hence the downstream cytokine inhibition could be increased. In conclusion, these results demonstrate the possibility to decrease the inflammatory reactions taken place in Alzheimer’s disease brains, which may ultimately lead to a possible way of controlling this disorder.
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Brooks, Lawrence G. "Adipose Tissue Cytokines: Effects of Social Condition." Scholarly Repository, 2009. http://scholarlyrepository.miami.edu/oa_dissertations/428.
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Social support has been demonstrated to reduce cardiovascular disease morbidity and mortality; however, the mechanisms by which social support reduces disease progression are still unclear. Oxytocin (OT) is a neuropeptide commonly associated with positive social interactions. This series of studies investigated the ability of oxytocin to attenuate atherosclerosis and its putative mediators, pro-inflammatory cytokines. Oxytocin receptors were identified by Western Blot on rat adipose tissue and rat adipocytes. OT receptor mRNA was identified in human adipocyte cDNA. In primary culture of rat abdominal adipocytes, oxytocin (10 pM) decreased LPS-induced IL-6 release by 24.9% after a six hour incubation. Adipose tissue, surgically dissected from ApoE-/- mice chronically infused with OT, secreted less IL-6 than mice infused with a vehicle control. In sum, the presence of OT receptors was demonstrated on adipocytes, OT was shown to reduce IL-6 release in vitro, and chronic OT infusion decreased IL-6 release in adipose explants immediately after sacrifice. Potential mechanisms by which adipose tissue's role in the sympathetic nervous system response may affect inflammation, metabolism, and disease are discussed.
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Yang, Huixin. "Role of cytokines in alveolar macrophage differentiation." Thesis, University of Ottawa (Canada), 1996. http://hdl.handle.net/10393/9918.
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The effects of macrophage colony-stimulating factor (M-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on rat alveolar macrophage (AM) differentiation in vitro were investigated in this study. Both M-CSF and GM-CSF triggered AM differentiation and multinucleated giant cell (MGC) formation. Morphological analysis further demonstrated that there were two distinct variants of MGC. Type 1 MGC normally contained 3 to 8 nuclei and appeared as a large round cell and type 2 MGC contained a higher number of nuclei (up to 30) and displayed irregular, elongated shapes. We also observed that a greater proportion of type 2 MGC expressed $\beta\sb3$ integrin, thus bringing additional evidence for differences between type 1 and type 2 MGC. Assessment of the relative proportion of type 1 and type 2 MGC indicated that M-CSF induced the formation of both types of MGC to a similar extent and GM-CSF induced predominantly the formation of type 2 MGC. Experiments with anti-M-CSF or anti-GM-CSF antibody to neutralize and cross-block the effects of M-CSF and GM-CSF further confirmed that M-CSF is associated with type 1 MGC formation whereas GM-CSF is responsible for type 2 MGC formation. Type 2 MGC seen in M-CSF treated groups may result from endogenous production of GM-CSF induced by M-CSF. This is supported by RT-PCR experiments in which M-CSF was shown to stimulate GM-CSF mRNA expression. Molecular phenotyping of a set of cytokines known to participate in inflammation and AM regulation was performed using RT-PCR at various times (up to 5 days) of AM differentiation. AM freshly obtained by BAL (0 time) did not show mRNA expression of TNF-$\alpha,$ IL-1$\alpha$ and IL-6, indicating these proinflammatory cytokines are not constitutively expressed by rat AM. Compared to the controls, both M-CSF and GM-CSF increased mRNA expression of TNF-$\alpha$ and IL-1$\alpha,$ suggesting these 2 cytokines are involved in M-CSF or GM-CSF induced AM differentiation. A significant increase of IL-6 mRNA expression was observed only in GM-CSF treated groups and the expression appeared early and persistently at all time points studied. Experiments with exogenous IL-6 and antibody to IL-6 receptor further indicated that IL-6 is involved in type 2 MGC formation. TGF-$\beta$ mRNA was constitutively expressed by rat AM and further enhanced by M-CSF and GM-CSF. Results from exogenous TGF-$\beta$ suggested that this cytokine favors formation of type 1 MGC over type 2 MGC. Cytoplasmic expression of TNF-$\alpha,$ PDGF and TGF-$\beta$ was investigated using immunocytochemical procedures. MGC were found to be able to express these cytokines, suggesting that MGC are a functional population rather than merely dead-end cells. Interestingly, type 1 MGC always showed higher levels of these cytokines than type 2 MGC, suggesting that type 1 MGC may be functionally more active than type 2 MGC.
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Giot, Jean-Philippe. "Implication des cytokines inflammatoires dans l'angiodermite nécrotique." Thesis, Poitiers, 2013. http://www.theses.fr/2013POIT1406/document.
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L'angiodermite nécrotique ou "Hypertensive Leg Ulcer" (HLU) est un ulcère de jambe inflammatoire de traitement difficile, associé à une hypertension artérielle chronique. La douleur est très importante et nécessite l'utilisation de la morphine pour soulager les patients. Notre objectif était d'analyser les caractéristiques de l'inflammation et d'étudier son implication dans la physiopathologie de la nécrose cutanée. La peau inflammatoire est le siège d'un infiltrat composé de macrophages et de lymphocytes. L'épiderme et les cellules vasculaires lisses des microvaisseaux présentent des troubles de la différenciation et une importante prolifération. Nous observé une forte augmentation des transcrits de l'interleukine 1β (IL-1β), de l'IL-6 et de l'Oncostatin M (OSM), qui sont exprimées par les macrophages.Les kératinocytes humains in vitro et in vivo chez la souris montrent un phénotype semblable lorsqu'ils sont exposés à ces cytokines.Comparée à la peau inflammatoire et à la peau saine, la peau en périphérie de l'inflammation est douloureuse et présente des altérations histologiques intermédiaires. On observe une légère augmentation de l'expression des cytokines inflammatoires IL-1β et OSM. D'autre part, la consommation de morphine est associée au niveau d'expression de l'OSM et l'inflammation systémique reflète la douleur ressentie par le patient. Ces éléments sont en faveur d'une implication des cytokines inflammatoires IL-1β et OSM dans la physiopathologie de la douleur et de la nécrose dans l'HLU. Le cercle vicieux pourrait être bloqué par l'utilisation des biothérapies anticytokines, ce qui met en avant de nouvelles cibles thérapeutiquesHypertensive Leg Ulcer (HLU) is an inflammatory skin lesion associated to chronic high blood pressure. The ulcer is painful requiring morphine to relieve patients. Our objective was to analyze the characteristics of the inflammation and to study it’s implication in pathogenesis of skin necrosis. Inflammatory skin is infiltrated by macrophages and lymphocytes. Keratinocytes and vascular smooth muscle cells of microvessels display an alteration of differentiation and an important proliferation. We studied the expression of cytokines associated to skin inflammation and we observed a strong augmentation of the transcripts for the interleukin 1β (IL-1β), the IL-6 and the Oncostatin M (OSM); which are expressed by the macrophages. The reconstructed human epidermis in vitro exposed to these cytokines showed a similar phenotype of the histological studies in human. At least, injection of these cytokines to the mouse produces an inflammation and an alteration of the epidermis comparable to HLU.Compared to the inflammatory skin and to the healthy skin, the skin in periphery of the inflammation is painful and presents intermediate histological alterations. We observed a slight augmentation of the inflammatory cytokines IL-1β and OSM. On the other hand, the consumption of morphine is associated with the level of expression of the OSM and systemic inflammation reflects the pain felt by the patient.The present evidence indicates an involvement of inflammatory cytokines IL-1β and OSM in the pathogenesis of pain and skin necrosis in the HLU. The vicious circle may be blocked by the use of biotherapies against inflammatory cytokines, which highlights new therapeutic targets
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Rahman, Arman. "Defensins and cytokines in inflammatory bowel disease." Doctoral thesis, Umeå : Univ, 2007. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-1377.
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Fisher, Linda. "Inflammatory cytokines and NFkB in Alzheimer's disease /." Stockholm : Department of Neurochemistry, Stockholm University, 2006. http://urn.kb.se/resolve?urn=urn:nbn:se:su:diva-990.
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Bueti, Deanna. "Immunomodulatory cytokines regulate intestinal epithelial barrier function /." Title page and abstract only, 2003. http://web4.library.adelaide.edu.au/theses/09SB/09sbb9289.pdf.
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Lazzerine, Abigail. "The role of cytokines in avian salmonellosis." Thesis, Imperial College London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.412579.
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Anwar, Ghazanfar Ali. "Genetic polymorphism in proinflammatory cytokines in bronchiectasis." Thesis, University of Newcastle Upon Tyne, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.576646.
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Bronchiectasis is a disease characterised by chronic bronchial sepsis and exerts considerable morbidity in those affected. In approximately 50% of cases the aetiology is unknown (idiopathic), raising the possibility of genetic predisposition. Cytokines such as IL-1, IL-6, IL-8 and TNFα are potent neutrophil recruiting molecules and are abundant in bronchiectatic secretions. Cytokine polymorph isms can lead to constitutively high production, and have been associated with a number of chronic inflammatory states. Hypothesis: Gene polymorph isms associated with high cytokine production predispose to idiopathic bronchiectasis (IB). Aims and objectives: To determine if high production alleles of cytokines IL-1β, IL6, IL8, TNF and IFNG are associated with idiopathic bronchiectasis (I B). Frequencies of these alleles were compared in patients with IB, bronchiectasis of known cause and normal controls. Allele frequencies in IB were also correlated with clinical markers of disease severity. Methods Following ethical approval, prospectively recruited patients underwent extensive clinical. phenotyping. IB was established as a diagnosis of exclusion. Allele frequencies for candidate genes were determined by PCR, with control allele frequencies available from local blood donors. Comparisons were made by Chi Square tests. Results: 189 patients (95f, 94m), mean (SO) age 66.11 (11.52) years were recruited including 82 (43%) idiopathies, No differences in the candidate allele frequencies were found between IB with 200+ controls and bronchiectasis of known cause group (n=1 06). Within idiopathic group, IL8+781T, IL6-174C, and IL1B-511T alleles were significantly associated with daily sputum production. In addition, IL8+781T and IL6-174C were associated with high exacerbation frequency and positive Pseudomonas aeruginosa culture. IL-1 B+3953T was significantly under- represented in those with daily sputum production and positive Pseudomonas status. Conclusions: Gene polymorphisms predisposing to high cytokine production were not found to be associated with lB. Several alleles were found to significantly associated with more severe disease. Independent confirmation is required in an adequately powered study.