IL-27 regulates autophagy in rheumatoid arthritis fibroblast-like synoviocytes via STAT3 signaling
IL-27 regulates autophagy in rheumatoid arthritis fibroblast-like synoviocytes via STAT3 signaling
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DOI：
10.1016/j.imbio.2022.152241
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发表时间：
2022-07-09
期刊：
影响因子：
2.8
通讯作者：
Gao, Wei
中科院分区：
文献类型：
--
作者：
Hou, Jiehong;Gao, Wei
风湿性关节炎（RA）是一种高度流行的自身免疫性疾病，与明显的滑膜炎症相关。大多数RA患者需要长期治疗以控制疾病进展，因此对受影响的个人造成了重大的经济负担。类风湿关节炎的发展受到滑膜内层成纤维细胞样滑膜细胞（FLS）的严重影响。IL-27是IL-6/IL-12家族细胞因子，最近已显示其在特定自身免疫性疾病中发挥各种促炎或保护作用。然而，IL-27在RA背景下对FLS的影响尚未得到澄清，需要进一步研究。本研究旨在评估IL-27治疗对RA相关FLS中细胞凋亡和自噬活性的影响，特别关注STAT 3通路在此调控背景下的作用。通过这些实验，我们发现IL-27能够抑制FLS增殖和自噬活性，高剂量的这种细胞因子（100 ng/mL）显著抑制自噬，同时诱导一定水平的细胞凋亡。STAT 3抑制剂STA 21被发现逆转IL-27介导的这些RA相关FLS中自噬活性的抑制。不平衡的细胞增殖和凋亡在RA进展的背景下是至关重要的，我们发现IL-27能够调节这种不平衡，并通过抑制雷帕霉素激活的自噬来增强RA FLS的凋亡活性。总之，这些结果表明IL-27可以通过STAT 3信号通路调节RA相关FLS内的自噬活性，从而抑制细胞增殖。
Rheumatoid arthritis (RA) is a highly prevalent autoimmune condition associated with pronounced synovial inflammation. The majority of RA patients required long-term treatment to control disease progression, thus imposing a significant financial burden on affected individuals. The development of RA is critically influenced by fibroblast-like synoviocytes (FLSs) within the synovial lining. IL-27 is an IL-6/IL-12 family cytokine that has recently been shown to play varied pro-inflammatory or protective roles in particular autoimmune diseases. However, the effects of IL-27 on FLSs in the context of RA have yet to be clarified and warrant further research. This study was developed to evaluate the impact of IL-27 treatment on apoptotic and autophagic activity in RA-associated FLSs, with a particular focus on the role of the STAT3 pathway in this regulatory context. Through these experiments, we found that IL-27 was able to suppress FLS proliferation and autophagic activity, with a high dose of this cytokine (100 ng/mL) markedly suppressing autophagy while simultaneously inducing some level of cellular apoptosis. The STAT3 inhibitor STA21 was found to reverse the IL-27-mediated suppression of autophagic activity in these RA-associated FLSs. Imbalanced cellular proliferation and apoptosis is of critical importance in the context of RA progression, and we found that IL-27 was able to regulate such imbalance and to enhance the apoptotic activity of RA FLSs by inhibiting rapamycin-activated autophagy. Together, these results indicate that IL-27 can regulate autophagic activity within RA-associated FLSs via the STAT3 signaling pathway, leading to inhibition of cellular proliferation.