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Ann Rheum Dis:HIF-1α激活天然免疫反应诱发类风湿关节炎的发病

2013-07-30 胡凡磊 北京青年报

近日,北京大学人民医院风湿免疫科主任栗占国教授课题组发现了类风湿关节炎新的发病机制。课题组研究发现,低氧和低氧诱导因子(HIF)-1α可激活天然免疫反应,诱发类风湿关节炎的发生。这使人们在细胞和分子水平上对类风湿关节炎的发病机制有了新的认识。这一新的发病机制的发现可以作为生物治疗的新靶点,有望成为类风湿关节炎领域的突破口。 该研究发现,在低氧条件下,细菌、病毒等天然感染可以刺激类风湿关节炎滑膜成

近日,北京大学人民医院风湿免疫科主任栗占国教授课题组发现了类风湿关节炎新的发病机制。课题组研究发现,低氧和低氧诱导因子(HIF)-1α可激活天然免疫反应,诱发类风湿关节炎的发生。这使人们在细胞和分子水平上对类风湿关节炎的发病机制有了新的认识。这一新的发病机制的发现可以作为生物治疗的新靶点,有望成为类风湿关节炎领域的突破口。

该研究发现,在低氧条件下,细菌、病毒等天然感染可以刺激类风湿关节炎滑膜成纤维细胞(RASF)分泌更多的炎性细胞因子白细胞介素以及肿瘤坏死因子等。正反两方面的研究证实,低氧诱导因子在这一过程中发挥着枢纽作用。进一步的功能研究揭示,RASF中HIF-1α的表达水平越高,其促进T细胞介导的炎症反应的能力越强,相应的类风湿关节炎病情也越严重。

此项研究在世界上首次证实了低氧及HIF-1α与toll样受体(TLR)通路两种作用方式在类风湿性关节炎发病过程中具有协同作用,该研究提示,“双管齐下”,同时应用阻断两个通路的药物将取得更好的治疗效果,改善类风湿关节炎预后。针对已取得的研究成果,课题组将进行临床前药物研究,以验证联合治疗的有效性。此外,课题组还将继续深入探讨HIF-1α在类风湿关节炎发病中的作用,以进一步诠释类风湿关节炎的发病机制。

原始出处:

Hu F, Mu R, Zhu J, Shi L, Li Y, Liu X, Shao W, Li G, Li M, Su Y, Cohen PL, Qiu X, Li Z.Hypoxia and hypoxia-inducible factor-1α provoke toll-like receptor signalling-induced inflammation in rheumatoid arthritis.Ann Rheum Dis. 2013 May 3.

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    2013-08-01 lmm397
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    2013-08-01 changfy
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    2013-08-01 wrj0126
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