NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways

Abstract

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease characterized by abnormal synovial hyperplasia and the release of inflammatory cytokines. NLRP12 is a member of the family nod-like receptor (NLR) families that are activators of inflammation. However, the role of NLRP12 in fibroblast-like synoviocytes (FLSs) is still unclear. In the present study, we have investigated the role of NLRP12 in fibroblast-like synoviocytes (FLSs). The results demonstrated that NLRP12 overexpression inhibited proliferation and promoted cell apoptosis in RA-FLSs. Moreover, NLRP12 overexpression repressed inflammation by downregulation of IL-1β, TNF-α, IL-6, IFN-γ and MCP-1 production and upregulation of IL-10 levels with knockdown of NLRP12 expression showing opposite effects. In addition, NLRP12 overexpression suppressed phosphorylation of JNK, ERK, p38 and NF-κB in RA-FLSs, whereas NLRP12 knockdown promoted phosphorylation of these proteins. In conclusion, these findings demonstrate that NLRP12 inhibits proliferation and inflammation of RA-FLSs via the regulation of the NF-κB and MAPK signaling pathways, suggesting that NLRP12 might be a potential target for RA treatment.