Study of the correlation between the noncanonical pathway of pyroptosis and idiopathic inflammatory myopathy

Abstract

Background: The pathogenesis of idiopathic inflammatory myopathy (IIM) is complex and unclear. The purpose of this study was to investigate whether the noncanonical pathway of pyroptosis is involved in the pathogenesis of IIM, and the intervention effect of drugs glyburide and bright blue G (BBG).

Methods: After the drug intervention, we detected the expression of the caspase-4, caspase-5, caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R proteins in skeletal muscle tissues from the six groups using Western blotting. We detected the expression of the caspase-11, GSDMD, pannexin-1, NLRP3 and P2X7R mRNAs in skeletal muscle tissues from the six groups using RT-qPCR and detected the serum IL-18 and IL-1β levels in the six groups using ELISAs.

Result: Lower expression levels of the P2X7R and NLRP3 proteins were observed in the EAM + BBG group than in the EAM1 group (P < 0.05). The expression of NLRP3 in the EAM + glyburide group was lower than in the EAM2 group (P < 0.05). Lower expression levels of the P2X7R and NLRP3 mRNAs were detected in the EAM + BBG group than in the EAM1 group (P < 0.05). NLRP3 was expressed at lower levels in the EAM + glyburide group than in the EAM2 group (P < 0.05). Lower serum IL-1β levels were detected in the EAM + BBG group than in the EAM1 group (P < 0.05), and serum IL-1β and IL-18 levels in the EAM + glyburide group were lower than those in the EAM2 group (P < 0.05).

Conclusion: Our results suggest that the noncanonical pathway of pyroptosis may be involved in the pathogenesis of IIM, and glyburide and BBG exert certain intervention effects on its pathogenesis.

Keywords: Experimental autoimmune myositis (EAM); Idiopathic inflammatory myopathy (IIM); Noncanonical pathway; Pyroptosis.