IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor
IL-6 inhibits the proliferation of fibroblastic synovial cells from rheumatoid arthritis patients in the presence of soluble IL-6 receptor
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DOI：
10.1093/intimm/12.2.187
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发表时间：
2000-02-01
影响因子：
4.4
通讯作者：
Yoshizaki, K
中科院分区：
文献类型：
--
作者：
Nishimoto, N;Ito, A;Yoshizaki, K
IL-6和肿瘤坏死因子(TNF)-α已被证明在类风湿性关节炎(RA)的发展中发挥重要作用，众所周知，TNF-α诱导滑膜细胞产生IL-6及其增殖。然而，IL-6 对滑膜细胞的影响尚不清楚。进行体外研究以确定IL-6对滑膜细胞增殖的影响。从八名 RA 患者的滑膜组织中分离出的成纤维细胞滑膜细胞在第三代至第六代后被使用。在可溶性 IL-6 受体 (sIL-6R) 存在下，IL-6 在 7 例病例中以剂量依赖性方式抑制滑膜细胞增殖，而不增加坏死或凋亡细胞的数量，而 TNF-α 在所有病例中均增加滑膜细胞增殖。尽管通过 RT-PCR 分析在这些细胞中检测到少量的 IL-6R，但仅在 sIL-6R 存在的情况下观察到 IL-6 的抑制作用。然而，抗IL-6R或抗gp130 mAb治疗增加了所有8个病例中滑膜细胞的自发生长，这表明滑膜细胞中表达的内源性IL-6和少量IL-6R在没有外源性IL-6或sIL-6R的情况下抑制了它们的生长。此外，IL-6-sIL-6R复合物减少了TNF-α诱导的滑膜细胞增殖，同时TNF-α诱导其IL-6产生。这些数据表明IL-6可能充当TNF-α诱导的滑膜细胞生长的负反馈因子。
IL-6 and tumor necrosis factor (TNF)-alpha have been proven to play an important role in the development of rheumatoid arthritis (RA), It is well known that TNF-alpha induces IL-6 production from synovial cells as well as their proliferation. The effect of IL-6 on synovial cells, however, is not clear. An in vitro study was performed to determine the effect of IL-6 on the proliferation of synovial cells. Fibroblastic synovial cells isolated from the synovial tissues of eight RA patients were employed after the third to sixth passages. IL-6 in the presence of soluble IL-6 receptor (sIL-6R) inhibited the proliferation of synovial cells in a dose-dependent manner in seven cases without increasing the number of necrotic or apoptotic cells, while TNF-alpha increased synovial cell proliferation in all cases. The inhibitory effect of IL-6 was observed only in the presence of sIL-6R although small amounts of IL-6R were detected in these cells by RT-PCR analysis. However, anti-IL-6R or anti-gp130 mAb treatment increased spontaneous growth of synovial cells in all eight cases, suggesting that endogenous IL-6 and a small amount of IL-6R expressed in synovial cells suppressed their growth without exogenous IL-6 or sIL-6R. In addition, the IL-6-sIL-6R complex reduced the TNF-alpha-induced proliferation of synovial cells while TNF-alpha induced their IL-6 production. These data suggest that IL-6 may act as a negative feedback factor for TNF-alpha-induced synovial cell growth.