Department of Rheumatology & Clinical Immunology, Qingdao University Affiliated Hospital, PR China.
Department of Rheumatology & Clinical Immunology, Qingdao University Affiliated Hospital, PR China.
Int Immunopharmacol. 2020 Nov;88:106985. doi: 10.1016/j.intimp.2020.106985. Epub 2020 Sep 17.
Rheumatoid arthritis (RA) is an inflammatory disease with symmetric polyarthritis. IL-6 and NLRP3 inflammasome in macrophages contribute to the pathogenesis of RA. This study aimed to investigate the relationship between IL-6 and the NLRP3 inflammasome in RA. Here, we found that IL-6 inhibition reduced NLRP3 inflammasome activation in mice with collage-induced arthritis (CIA). In vitro studies showed that IL-6 directly induced NLRP3 inflammasome activation via cathepsin B (CTSB) in the presence of ATP. In addition, S100A9 induced by ATP stimulation promoted the interaction of CTSB and NLRP3 to activate the NLRP3 inflammasome. Our findings show a novel mechanism of NLRP3 inflammasome activation by IL-6 that may lead to a potential therapy for RA by interrupting the interaction between IL-6 and the NLRP3 inflammasome.
类风湿关节炎（RA）是一种以对称性多关节炎为特征的炎症性疾病。巨噬细胞中的白细胞介素 6（IL-6）和 NOD 样受体热蛋白 3（NLRP3）炎性小体参与了 RA 的发病机制。本研究旨在探讨 RA 中 IL-6 与 NLRP3 炎性小体的关系。在这里，我们发现 IL-6 抑制可减少胶原诱导性关节炎（CIA）小鼠中 NLRP3 炎性小体的激活。体外研究表明，在存在 ATP 的情况下，IL-6 通过组织蛋白酶 B（CTSB）直接诱导 NLRP3 炎性小体的激活。此外，ATP 刺激诱导的 S100A9 促进 CTSB 与 NLRP3 的相互作用，从而激活 NLRP3 炎性小体。我们的研究结果表明，IL-6 通过一种新的机制激活 NLRP3 炎性小体，通过阻断 IL-6 与 NLRP3 炎性小体的相互作用，可能为 RA 的治疗提供一种新的策略。
