Cyr61 participates in the pathogenesis of rheumatoid arthritis by promoting proIL-1β production by fibroblast-like synoviocytes through an AKT-dependent NF-κB signaling pathway

Clinical Immunology : the Official Journal of the Clinical Immunology Society
Xianjin ZhuNingli Li

Abstract

IL-1β plays a major role in the development of rheumatoid arthritis (RA). We previously showed that Cyr61 participates in RA pathogenesis as a proinflammatory factor. Here, we found that the levels of IL-1β and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1β mRNA and proIL-1β protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1β was hardly detectable in the supernatant. We also found that the level of adenosine triphosphate (ATP) in SF and ST was significantly increased in RA patients and that the level of IL-1β in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1β production in FLS via the AKT-dependent NF-κB signaling pathway, and ATP caused Cyr61-induced proIL-1β to generate IL-1β in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1β production in FLS.

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Citations

Jun 14, 2017·Journal of Molecular Recognition : JMR·Chen ZhongJianping Ding
Jan 30, 2018·Cellular & Molecular Immunology·Haijing WuQianjin Lu
Nov 8, 2017·Cell Proliferation·Zheng LiWilliam K K Wu
Mar 14, 2018·International Journal of Molecular Medicine·Yun ZhangYunfeng Yang
Jul 29, 2016·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Cheng-Yu ChenChih-Hsin Tang
May 23, 2019·Arthritis Research & Therapy·Yong FanZhuoli Zhang
Aug 11, 2020·Mediators of Inflammation·Mi ZhouXin Li
May 1, 2021·International Journal of Molecular Sciences·Iona J MacDonaldChih-Hsin Tang
May 15, 2021·Immunological Reviews·Ronen SchusterBoris Hinz
Jul 7, 2021·Journal of Cell Communication and Signaling·Veronica Giusti, Katia Scotlandi

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