Chang Le, Feng Xin, Gao Wei
a Department of Rheumatoid Immunity , the First Affiliated Hospital of Jinzhou Medical University , Jinzhou , Liaoning , China.
Connect Tissue Res. 2019 Jul;60(4):358-366. doi: 10.1080/03008207.2018.1552266. Epub 2018 Dec 4.
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 20 ng/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.
成纤维样滑膜细胞（FLS）具有肿瘤样增殖特性，在类风湿关节炎（RA）中发挥重要作用，而白细胞介素-17（IL-17）通过影响FLS参与RA病理过程。本研究旨在探讨IL-17对FLS增殖和自噬的影响以及信号转导和转录激活因子3（STAT3）在RA中的作用。用不同浓度（0、1、10和20 ng/mL）的IL-17处理FLS；然后，通过蛋白质免疫印迹法、免疫荧光法和透射电子显微镜检测自噬。用细胞计数试剂盒-8法检测IL-17对FLS增殖的影响，并用流式细胞术分析细胞周期分布，通过蛋白质免疫印迹法检测增殖细胞核抗原（PCNA）。使用自噬抑制剂3-甲基腺嘌呤（3-MA）和氯喹（CQ）确定自噬对IL-17处理的FLS增殖的影响。最后，使用STAT3抑制剂STA21检测IL-17处理的FLS中STAT3与自噬之间的关系。我们的结果表明，IL-17对FLS的自噬和增殖有正向影响。抑制自噬可抑制IL-17介导的FLS增殖。此外，抑制STAT3激活可降低IL-17处理的FLS中的自噬。我们的研究结果表明，IL-17通过激活STAT3上调自噬促进FLS的肿瘤样增殖。
