Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis
Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis
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DOI：
10.1006/cyto.2000.0681
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发表时间：
2000-07-01
期刊：
影响因子：
3.8
通讯作者：
Miossec, P
中科院分区：
文献类型：
--
作者：
Chabaud, M;Garnero, P;Miossec, P
白细胞介素17(IL-17)是一种由RA滑膜产生的T细胞来源的促炎细胞因子，我们研究了IL-17在滑膜细胞因子网络中的作用，以确定其是否能影响RA的炎症和破坏性模式特征。在此，我们研究了IL-17在促炎细胞因子(IL-1)和抗炎细胞因子(IL-4、IL-13、IL-10)存在的情况下是否能调节基质金属蛋白酶-1及其抑制物TIMP-1的产生和作用，以及阻断内源性IL-17对Iu滑膜分泌MMP1和TIMP-1及基质破坏的影响。IL-17使滑膜细胞自发产生的基质金属蛋白酶-1增加5倍。在IL-17或IL-1β刺激滑膜细胞产生TIMP-1的同时，加入IL-4、IL-13和IL-10可减少滑膜细胞自发产生的基质金属蛋白酶-1，并诱导滑膜细胞产生TIMP-1。在抗IL-17阻断单抗的存在下，RA滑膜产生的基质金属蛋白酶-1和胶原酶活性减少50%，同时滑膜上清液中释放的I型胶原C-端肽片段(CTS)减少50%，说明IL-17对滑膜细胞的破坏有直接作用。IL-17及其产生的T细胞似乎参与了类风湿病变所涉及的炎症过程。(C)。2000年学术出版社。
Interleukin (IL-)17 is a T cell-derived pro-inflammatory cytokine produced by RA synovium, We studied the role of IL-17 in the synovium cytokine network to determine whether it can influence the inflammatory and destructive pattern characteristic of RA. Herein, we investigated whether the production and action of MMP-1 and its inhibitor TIMP-1 could be modulated by IL-17 in the presence of pro-inflammatory cytokine (IL-1) and anti-inflammatory cytokines (IL-4, IL-13, IL-10), The effect of the blockade of endogenous IL-17 on the secretion of MMP-1 and TIMP-1 by IU synovium and matrix destruction was also studied. IL-17 increased the spontaneous production of MMP-1 by synoviocytes five-fold. IL-1 was more potent since it increased MMP-1 production nine-fold, Addition of IL-4, IL-13 and IL-10 to synoviocyte cultures reduced the spontaneous production of MMP-1 and induced TIMP-1 production by synoviocytes stimulated with IL-17 or/and IL-1 beta In the presence of anti-IL-17 blocking mAb, MMP-1 production and collagenase activity by RA synovium was reduced by 50% and associated with a 50% reduction in type I collagen C-telopeptide fragments (CTS) released in the supernatants, demonstrating the direct contribution of IL-17 in destruction. IL-17 and its producing T cells appear to contribute to the inflammatory process involved in the rheumatoid lesion. (C). 2000 Academic Press.