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.
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Xin Zhang and He Nan designed the study and supervised the data collection, Jinyu Liu analyzed and interpreted the data, and Jialong Guo prepared the manuscript for publication and reviewed the draft of the manuscript. All the authors have read and approved the manuscript.
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Ethical approval was obtained from the Ethics Committee of China-Japan Union Hospital of Jilin University.
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Zhang, X., Nan, H., Guo, J. et al. NLRP12 reduces proliferation and inflammation of rheumatoid arthritis fibroblast-like synoviocytes by regulating the NF-κB and MAPK pathways. Eur Cytokine Netw 32, 15–22 (2021). https://doi.org/10.1684/ecn.2021.0465
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DOI: https://doi.org/10.1684/ecn.2021.0465