Yang Ru, Zhang Yingzi, Wang Lin, Hu Ji, Wen Jian, Xue Leixi, Tang Mei, Liu Zhichun, Fu Jinxiang
Department of Rheumatology, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
Department of Orthopaedics, The Second Affiliated Hospital to Soochow University, Jiangsu, China.
Oncotarget. 2017 Feb 28;8(9):15420-15430. doi: 10.18632/oncotarget.14331.
The incidence of rheumatoid arthritis (RA) has been reported to be correlated with a disorder of immunregulation. Rheumatoid arthritis fibroblast-like synoviocytes (RA-FLSs) play an important role in regulating the local immune microenvironment. However, the potential mechanism of RA-FLS in regulating the immnue response is not clearly understood. In this study, we demonstrated that the expression of HIF-1α was significantly up-regulated in rheumatoid arthritis tissue which indicated that the hypoxia condition in the microenvironment. We also observed that RA-FLSs demonstrated the potential to up-regulate immune activation. Meanwhile, the level of autophagy increased in RA-FLSs compared with control group. Besides that, the expression of IL-6 was up-regulated not only in RA-FLSs but also in the fibroblasts that treated with hypoxia condition. Accordingly, we found that autophagy inhibitiors could effectively inhibit the immune activation function of RA-FLSs medicated by IL-6. Taken together, the results we demonstrated above indicated that the hypoxia microenvironment could effectively induce the incidence of autophagy and then lead to the immune activation function of RA-FLSs medicated by IL-6.
据报道，类风湿性关节炎（RA）的发病率与免疫调节紊乱相关。类风湿关节炎成纤维样滑膜细胞（RA-FLSs）在调节局部免疫微环境中起重要作用。然而，RA-FLS调节免疫反应的潜在机制尚不清楚。在本研究中，我们证明类风湿关节炎组织中HIF-1α的表达显著上调，这表明微环境中存在缺氧情况。我们还观察到RA-FLSs具有上调免疫激活的潜力。同时，与对照组相比，RA-FLSs中的自噬水平增加。此外，IL-6的表达不仅在RA-FLSs中上调，而且在用缺氧条件处理的成纤维细胞中也上调。因此，我们发现自噬抑制剂可以有效抑制IL-6介导的RA-FLSs的免疫激活功能。综上所述，我们上述结果表明，缺氧微环境可有效诱导自噬的发生，进而导致IL-6介导的RA-FLSs的免疫激活功能。
