期刊
JOURNAL OF IMMUNOLOGY
卷 191, 期 3, 页码 1364-1372出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1300274
关键词
-
类别
资金
- Dutch Arthritis Association
Th17 cells are critically involved in autoimmune disease induction and severity. Recently, we showed that Th17 cells from patients with rheumatoid arthritis (RA) directly induced a proinflammatory loop upon interaction with RA synovial fibroblasts (RASF), including increased autocrine IL-17A production. To unravel the mechanism driving this IL-17A production, we obtained primary CD4(+)CD45RO(+)CCR6(+) (Th17) cells and CD4(+)CD45RO(+) CCR6(-) (CCR6(-)) T cells from RA patients or healthy individuals and cocultured these with RASF. IL-1 beta, IL-6, IL-23p19, and cyclooxygenase (COX)-2 expression and PGE(2) production in Th17-RASF cultures were higher than in CCR6(-) T cell-RASF cultures. Cytokine neutralization showed that IL-1 beta and IL-6, but not IL-23, contributed to autocrine IL-17A induction. Importantly, treatment with celecoxib, a COX-2 inhibitor, resulted in significantly lower PGE(2) and IL-17A, but not IFN-gamma, production. Combined celecoxib and TNF-alpha blockade more effectively suppressed the proinflammatory loop than did single treatment, as shown by lower IL-6, IL-8, matrix metalloproteinase-1 and matrix metalloproteinase-3 production. These findings show a critical role for the COX-2/PGE(2) pathway in driving Th17-mediated synovial inflammation in an IL-23- and monocyte-independent manner. Therefore, it would be important to control PGE(2) in chronic inflammation in RA and potentially other Th17-mediated autoimmune disorders.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据