1. Academic Validation
  2. IL-6 promotes collagen-induced arthritis by activating the NLRP3 inflammasome through the cathepsin B/S100A9-mediated pathway

IL-6 promotes collagen-induced arthritis by activating the NLRP3 inflammasome through the cathepsin B/S100A9-mediated pathway

  • Int Immunopharmacol. 2020 Nov;88:106985. doi: 10.1016/j.intimp.2020.106985.
Hongyue Wang 1 Ziye Wang 1 Liqin Wang 1 Linqian Sun 1 Wenping Liu 1 Qing Li 1 Jibo Wang 2
Affiliations

Affiliations

  • 1 Department of Rheumatology & Clinical Immunology, Qingdao University Affiliated Hospital, PR China.
  • 2 Department of Rheumatology & Clinical Immunology, Qingdao University Affiliated Hospital, PR China. Electronic address: 2017021773@qdu.edu.cn.
Abstract

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.

Keywords

ATP; IL-6; NLRP3 inflammasome; Rheumatoid arthritis; S100A9.

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