Proliferation of rheumatoid arthritis fibroblast-like synoviocytes is enhanced by IL-17-mediated autophagy through STAT3 activation.

Fibroblast-like synoviocytes (FLSs), with their tumor-like proliferation, play an important role in rheumatoid arthritis (RA), and interleukin-17 (IL-17) participates in RA pathology by affecting FLSs. The aims of this study were to investigate the effects of IL-17 on the proliferation and autophagy of FLSs and the role of signal transducer and activator of transcription-3 (STAT3) in RA. FLSs were treated with IL-17 at different concentrations (0, 1, 10, and 20ng/mL); then, autophagy was assayed with western blotting, immunofluorescence, and transmission electron microscopy. The effects of IL-17 on FLSs proliferation were measured with the Cell Counting Kit-8 assay and flow cytometry to analyze cell cycle distribution, and proliferating cell nuclear antigen (PCNA) was detected by western blotting. The autophagy inhibitors, 3-methyladenine (3-MA) and chloroquine (CQ), were used to determine the effect of autophagy on proliferation in IL-17-treated FLSs. Finally, the STAT3 inhibitor STA21 was used to examine the relationship between STAT3 and autophagy in IL-17-treated FLSs. Our results showed that IL-17 positively affected autophagy and proliferation in FLSs. Inhibition of autophagy suppressed the IL-17-mediated proliferation of FLSs. Additionally, suppression of STAT3 activation decreased autophagy in IL-17-treated FLSs. Our findings showed that IL-17 promoted the tumor-like proliferation of FLSs by upregulating autophagy via STAT3 activation.