期刊
FRONTIERS IN IMMUNOLOGY
卷 7, 期 -, 页码 -出版社
FRONTIERS MEDIA SA
DOI: 10.3389/fimmu.2016.00532
关键词
TGF-beta 1; HIF-1 alpha; succinate; NLRP3 inflammasome; synovial fibrosis; collagen-induced arthritis; clematichinenoside AR
类别
资金
- National Natural Science Foundation of China [81473396, 81403057]
- priority academic program development of Jiangsu higher education institutions (PAPD)
Clematichinenoside AR (C-AR) is a triterpene saponin isolated from the root of Clematis manshurica Rupr., which is a herbal medicine used in traditional Chinese medicine for the treatment of arthritis. C-AR exerts anti-inflammatory and immunosuppressive properties, but little is known about its action in the suppression of fibroblast activation. Low oxygen tension and transforming growth factor-beta (TGF-beta 1) induction in the synovium contribute to fibrosis in arthritis. This study was designed to investigate the effect of C-AR on synovial fibrosis from the aspects of hypoxic TGF-beta 1 and hypoxia-inducible transcription factor-1 alpha (HIF-1 alpha) induction. In the synovium of rheumatoid arthritis (RA) rats, hypoxic TGF-beta 1 induction increased succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activation and induced NLRP3 inflammasome activation in a manner dependent on HIF-1 alpha induction. In response to NLRP3 inflammasome activation, the released IL-1 beta further increased TGF-beta 1 induction, suggesting the forward cycle between inflammation and fibrosis in myofibroblast activation. In the synovium of RA rats, C-AR inhibited hypoxic TGF-beta 1 induction and suppressed succinate- associated NLRP3 inflammasome activation by inhibiting SDH activity, and thereby prevented myofibroblast activation by blocking the cross-talk between inflammation and fibrosis. Taken together, these results showed that succinate worked as a metabolic signaling, linking inflammation with fibrosis through NLRP3 inflammasome activation. These findings suggested that synovial succinate accumulation and HIF-1 alpha induction might be therapeutical targets for the prevention of fibrosis in arthritis.
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