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

IL-1 beta 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-1 beta and Cyr61 were higher in RA SF than in osteoarthritis (OA) SF. IL-1 beta mRNA and proIL-1 beta protein levels were remarkably increased in Cyr61-stimulated FLS; however, IL-1 beta 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-1 beta in supernatants from Cyr61-activated FLS increased significantly when we added exogenous ATP to the culture. Mechanistically, Cyr61 induced proIL-1 beta production in FLS via the AKT-dependent NF-kappa B signaling pathway, and ATP caused Cyr61-induced proIL-1 beta to generate IL-1 beta in a caspase-1-dependent manner. Our results reveal a novel role of Cyr61 in RA that involves the promotion of proIL-1 beta production in FLS. (C) 2015 Elsevier Inc. All rights reserved.