Inhibition of C5a Prevents Il-1β-Induced Alternations in Rat Synoviocytes in Vitro

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  • 作者:Lu, W., Wang, L., Yao, J., Wang, W. & Chen, Y.
  • 期刊:Molecular and cellular probes 41, 14-21 (2018)
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C5a is an important pro-inflammatory peptide involved in complement activation, membrane attack complex formation, immune cell chemotaxis, and allergic responses. Osteoarthritis is a disease characterized by degenerative changes in articular cartilage. It has recently been found that inflammatory responses play an important role in the pathogenesis of osteoarthritis and also in rheumatoid arthritis, where dysfunctional synoviocytes are involved. We performed a series of studies to verify our hypothesis that inhibition of C5a would prevent IL-1β-induced alternations in rat synoviocytes. In vitro studies were performed with RSC-364?cells to examine the role of C5a in the function of synoviocytes. RSC-364?cells (a rat derived synovial cell line) were treated with IL-1β, IL-1β+siC5a, IL-1β+PMX205 that is antagonist of C5aR, or left untreated. Cell cycle, proliferation, apoptosis, invasion, as well as levels of C5a, IL-17A and TNF-α expression were evaluated. We found that IL-1β could significantly increase the proliferation and invasion capabilities of RSC-364?cells, as well as of C5a IL-17A and TNF-α expression. In contrast, inhibition of C5a by siRNA or application of antagonist of C5aR PMX205 reversed the IL-1β-induced changes in C5a expression, cell cycle, proliferation, apoptosis, invasion, and cytokines releases. Taken together, our study results suggest that IL-1β can increase C5a expression in RSC-364?cells, and that C5a exerts a proinflammatory effect in RSC-364?cells. Inhibition of C5a might represent a new strategy for treating rheumatoid arthritis.

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