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IL-27誘導人成纖維樣滑膜細胞產(chǎn)生IL-6的機制研究

發(fā)布時間:2018-04-14 14:33

  本文選題:IL-27 + 類風濕關節(jié)炎; 參考:《重慶醫(yī)科大學》2017年碩士論文


【摘要】:目的:類風濕關節(jié)炎是一種以關節(jié)軟骨損傷和關節(jié)滑膜炎癥為病理特征的炎癥性自身免疫性疾病。成纖維樣滑膜細胞是關節(jié)滑膜里的一種間充質細胞,在類風濕關節(jié)炎的免疫發(fā)病機制中發(fā)揮著重要的作用。活化的成纖維樣滑膜細胞可以產(chǎn)生大量的可溶性的和結合于細胞表面的炎癥介質分子,這些炎癥介質能導致炎癥加劇和組織的破壞。但是,調節(jié)成纖維樣滑膜細胞釋放各種炎癥介質的分子機制目前尚未闡述清楚。本研究擬探討白介素27(Interleukin-27,IL-27)對人成纖維樣滑膜細胞(Human fibroblast-like synoviocyte,HFLS)的體外活化效應及細胞內信號傳導途徑。方法:IL-27刺激人成纖維樣滑膜細胞48小時后,ELISA檢測細胞培養(yǎng)上清液中IL-6水平的變化;用信號通路抑制劑處理FLS 1小時后,再用IL-27刺激FLS 48小時,ELISA檢測細胞上清液中IL-6的水平變化;IL-27刺激FLS不同時間點,western blot檢測細胞內信號通路蛋白的磷酸化水平。結果:IL-27能刺激正常關節(jié)來源的人FLS和RA患者關節(jié)來源的人FLS產(chǎn)生IL-6水平顯著升高,且具有時間和劑量依賴性。IL-27能刺激人FLS細胞內信號通路蛋白JAK-2和JNK的磷酸化水平升高。JAK抑制劑AG490和JNK抑制劑SP600125可明顯抑制IL-27誘導FLS產(chǎn)生IL-6。結論:IL-27通過激活人FLS細胞內JAK-2和JNK信號通路,從而上調FLS分泌產(chǎn)生IL-6水平,由此說明細胞因子IL-27在類風濕關節(jié)炎的發(fā)病機制中扮演著重要的促炎癥作用。
[Abstract]:Objective: rheumatoid arthritis is an inflammatory autoimmune disease characterized by articular cartilage injury and synovitis.Fibroblast is a kind of mesenchymal cells in synovium, which plays an important role in the immune pathogenesis of rheumatoid arthritis.Activated fibroblast synovial cells can produce a large number of soluble and bound to the surface of the cell surface of inflammatory molecules, these inflammatory mediators can lead to increased inflammation and tissue destruction.However, the molecular mechanisms regulating the release of various inflammatory mediators by fibroid synovial cells have not been clarified.The aim of this study was to investigate the in vitro activation and intracellular signaling pathway of interleukin-27 interleukin-27 (IL-27) on human fibroblast synoviocyte (HFLs) in human fibroblast synoviocytes.Methods the level of IL-6 in the supernatant of cultured human fibroblasts was detected by Elisa after stimulation of human fibroblast synoviocytes by 1: IL-27 for 48 hours, and FLS was treated with signal pathway inhibitor for 1 hour.IL-27 stimulated FLS for 48 hours was used to detect the level of IL-6 in the supernatant. IL-27 stimulated FLS at different time points and western blot was used to detect the phosphorylation level of intracellular signal pathway protein.Results: the level of IL-6 was significantly increased in human FLS from normal joints and FLS in patients with RA.In a time and dose-dependent manner, IL-27 could increase the phosphorylation level of JAK-2 and JNK in human FLS cells. AG490, a JAK inhibitor, and SP600125, an inhibitor of JNK, could significantly inhibit IL-27 induced production of IL-6 in FLS.Conclusion by activating the JAK-2 and JNK signaling pathways in human FLS cells, the cytokine IL-27 up-regulates the secretion of FLS to produce IL-6, which suggests that the cytokine IL-27 plays an important role in promoting inflammation in the pathogenesis of rheumatoid arthritis.
【學位授予單位】:重慶醫(yī)科大學
【學位級別】:碩士
【學位授予年份】:2017
【分類號】:R593.22

【參考文獻】

相關期刊論文 前1條

1 賴曉霏;張莉萍;;類風濕關節(jié)炎患者血清中IL-27、炎癥指標和疾病活動度的相關性分析[J];免疫學雜志;2014年06期



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