NLRC3 alleviates immune inflammatory response induced by macrophage pyroptosis in patients with rheumatoid arthritis by inhibiting STING signaling pathway
Objective To explore the role and potential mechanism of caspase activation and recruitment domain-containing nucleotide-binding oligomerization domain-like receptor 3(NLRC3)in the immune inflammatory response induced by macrophage pyroptosis in patients with rheumatoid arthritis(RA).Methods Fifty RA patients and ten healthy volunteers were selected according to inclusion criteria.Peripheral blood macrophages were extracted and divided into six groups:normal control(NC),RA macrophage model(RA-MC),RA-MC with NLRC3 overexpression,RA-MC with NLRC3 knockdown,RA-MC with STING overexpression,and RA-MC with STING knockdown groups.Macrophage pyroptosis was observed using transmission electron microscopy.The mRNA expressions of NLRC3,STING,caspase-1,and GSDMD were detected using RT-qPCR.interleukin 1β(IL-1β)and IL-18 levels in cell supernatants were measured using ELISA.Results Compared to the NC group,the RA-MC group showed characteristics of pyroptosis.Compared to the RA-MC group,the groups of RA-MC with NLRC3 overexpression and RA-MC with STING knockdown showed improved pyroptosis,while the groups of RA-MC with NLRC3 knockdown and RA-MC with STING overexpression demonstrated exacerbated pyroptosis.Compared to the NC group,the RA-MC group showed increased mRNA expression levels of STING,caspase-1 and GSDMD,as well as increased levels of the inflammatory cytokines IL-1β and IL-18,but decreased NLRC3 mRNA expression level.Compared to the RA-MC group,the groups of RA-MC with NLRC3 overexpression and RA-MC with STING knockdown showed reduced mRNA expression levels of caspase-1 and GSDMD,as well as reduced inflammatory factors,while the groups of RA-MC with NLRC3 knockdown and RA-MC with STING overexpression had opposite results.Compared to the RA-MC group,the group of RA-MC with NLRC3 overexpression showed a decreased STING mRNA expression level,while the group of RA-MC with NLRC3 knockdown demonstrated an increased level.Conclusion NLRC3 can inhibit the STING signaling pathway,reduce pyroptosis proteins caspase-1 and GSDMD,antagonize macrophage pyroptosis,and lower the levels of inflammatory cytokines IL-1β and IL-18,thereby alleviating the immune inflammatory response in RA patients.
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