本文選題：IL-27 + 類風(fēng)濕關(guān)節(jié)炎�。� 參考：《重慶醫(yī)科大學(xué)》2017年碩士論文

【摘要】：目的:類風(fēng)濕關(guān)節(jié)炎是一種以關(guān)節(jié)軟骨損傷和關(guān)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(xì)胞是關(guān)節(jié)滑膜里的一種間充質(zhì)細(xì)胞,在類風(fēng)濕關(guān)節(jié)炎的免疫發(fā)病機(jī)制中發(fā)揮著重要的作用�；罨某衫w維樣滑膜細(xì)胞可以產(chǎn)生大量的可溶性的和結(jié)合于細(xì)胞表面的炎癥介質(zhì)分子,這些炎癥介質(zhì)能導(dǎo)致炎癥加劇和組織的破壞。但是,調(diào)節(jié)成纖維樣滑膜細(xì)胞釋放各種炎癥介質(zhì)的分子機(jī)制目前尚未闡述清楚。本研究擬探討白介素27(Interleukin-27,IL-27)對(duì)人成纖維樣滑膜細(xì)胞(Human fibroblast-like synoviocyte,HFLS)的體外活化效應(yīng)及細(xì)胞內(nèi)信號(hào)傳導(dǎo)途徑。方法:IL-27刺激人成纖維樣滑膜細(xì)胞48小時(shí)后,ELISA檢測(cè)細(xì)胞培養(yǎng)上清液中IL-6水平的變化;用信號(hào)通路抑制劑處理FLS 1小時(shí)后,再用IL-27刺激FLS 48小時(shí),ELISA檢測(cè)細(xì)胞上清液中IL-6的水平變化;IL-27刺激FLS不同時(shí)間點(diǎn),western blot檢測(cè)細(xì)胞內(nèi)信號(hào)通路蛋白的磷酸化水平。結(jié)果:IL-27能刺激正常關(guān)節(jié)來(lái)源的人FLS和RA患者關(guān)節(jié)來(lái)源的人FLS產(chǎn)生IL-6水平顯著升高,且具有時(shí)間和劑量依賴性。IL-27能刺激人FLS細(xì)胞內(nèi)信號(hào)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(dǎo)FLS產(chǎn)生IL-6。結(jié)論:IL-27通過(guò)激活人FLS細(xì)胞內(nèi)JAK-2和JNK信號(hào)通路,從而上調(diào)FLS分泌產(chǎn)生IL-6水平,由此說(shuō)明細(xì)胞因子IL-27在類風(fēng)濕關(guān)節(jié)炎的發(fā)病機(jī)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(xué)位授予單位】：重慶醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R593.22

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 賴曉霏;張莉萍;;類風(fēng)濕關(guān)節(jié)炎患者血清中IL-27、炎癥指標(biāo)和疾病活動(dòng)度的相關(guān)性分析[J];免疫學(xué)雜志;2014年06期

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本文編號(hào)：1749766