GRIM19 downregulation induced macrophages pyroptosis through NLRP3 pathway in adenomyosis

Abstract Adenomyosis is a common benign gynecological disease. The endometrium of adenomyosis is infiltrated by a large number of macrophages, and secretion of IL1B is significantly improved, but the underlying mechanisms remain unclear. The aim of this study was to investigate the correlations with GRIM19 expression and pyroptosis mediated by NLRP3, and to explain whether the release of IL1B resulted by pyroptosis is a relevant factor in the regulation of adenomyosis progression. In this study, we showed that the expression of GRIM19 was significantly lower in adenomyosis. In THP-1-derived macrophages, NLPR3, ASC, caspase1, GSDMD, and IL1B production are unregulated after downregulation of GRIM19. GRIM19 knockdown induced the release of IL1B in THP-1-derived macrophages. The HESC cell were co-cultured with GRIM19-depleted macrophages and IL1B neutralizing antibody was used to detect the effects of macrophages pyroptosis on apoptosis, proliferation and migration of HESC. The apoptosis of HESC co-cultured with GRIM19 knockdown macrophages was significantly inhibited, the proliferation and migration were markedly promoted. While existence of IL1B neutralize antibody in supernatants recovered the effects of GRIM19 knockdown macrophages on HESC. In conclusion, this study suggests that GRIM19 downregulation induces macrophages pyroptosis through NLRP3 pathway, increases the secretion of IL1B and promotes adenomyosis progression.