Abstract:

Objective Traditional Chinese medicine chloroquine（CQ）has been used as one of the main drugs for rheumatoid arthritis treatment，but its mechanism of action is still unclear. This study investigated the inhibitory effect of CQ on the activation of fibroblast⁃like synoviocyte（FLS）in rheumatoid arthritis and its molecular mechanism. Methods MH7A cells were pre⁃stimulated by TNF⁃α to establish a FLS activation model for rheuma⁃ toid arthritis. The effects of CQ on MH7A cell proliferation，pro⁃inflammatory cytokines IL⁃6 and CXCL10，and invasion proteins MMP⁃2 and MMP⁃9 were detected. Then，TRAF3 expression and autophagy in MH7A cells were evaluated after CQ treatment. Afterward，TRAF3 was down⁃regulated by siRNA and autophagy was induced by rapamycin to examine the role of TRAF3 in CQ ⁃induced inhibition of FLS activation and its mechanism. Results CQ effectively inhibited the proliferation of MH7A cells ，decreased the secretion of IL⁃6 and CXCL10 ，and reduced MMP⁃2 and MMP⁃9 expression. CQ did not up⁃regulate TRAF3 expression，but increased TRAF3 protein content. And the TRAF3 mediated the CQ⁃induced inhibition on FLS activation. CQ inhibited autophagy，while rapamycin reduced TRAF3 protein levels and antagonized the inhibition of chloroquine on FLS activation. Conclusion CQ can increase the TRAF3 protein in FLS by inhibiting autophagic degradation，and inhibit the abnormal activation of FLS in rheumatoid arthritis via TRAF3.

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