GRIM19 downregulation-induced pyroptosis of macrophages through NLRP3 pathway in adenomyosis

Haoran Liu, Liu H, Zhao Y, Yue Zhao, Yang Y, Yang Yang, Wenqian Huang, Huang W, Lan Chao, Chao L, Chao Lan
Reproductive biomedicine online · 2021 · vol. 44(2) , pp. 211–219 · doi:10.1016/j.rbmo.2021.10.012 · PMID:34906422 · W3210874855
article OA: closed CC0 ⤵ 3 in-corpus citations
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This study investigated how GRIM19 downregulation triggers pyroptosis in macrophages via the NLRP3 pathway, contributing to adenomyosis pathology.

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Abstract

Research questionDoes the absence of GRIM19 affect pyroptosis of macrophages? Is the release of IL-1β caused by pyroptosis a relevant factor in the regulation of adenomyosis progression?DesignEndometrial tissues were collected from patients with (n = 12) and without (n = 12) adenomyosis. GRIM19 expression of adenomyosis tissues was analysed by western blot and real-time polymerase chain reaction (RT-PCR). In GRIM19 knockdown macrophages, pyroptosis-related factors expressions were also measured by western blot and RT-PCR. The human endometrial stromal cells (HESC) were co-cultured with GRIM19-depleted macrophages and IL-1β neutralizing antibody to detect the effects of pyroptosis of macrophages on apoptosis, proliferation and migration of HESC.ResultsThe expression of GRIM19 was significantly lower in adenomyosis (P = 0.0002). In THP-1-derived macrophages, the expression of NLRP3 (P < 0.0001), ASC (P = 0.0176), caspase-1 (P = 0.0368), GSDMD (P = 0.0453) and IL-1β (P = 0.0208) are increased after downregulation of GRIM19. GRIM19 knockdown induced the release of IL-1β (P = 0.0195) in THP-1-derived macrophages. The apoptosis of HESC co-cultured with GRIM19 knockdown macrophages was significantly inhibited (P < 0.0001), the proliferation (P = 0.0254) and migration (P < 0.0001) were markedly promoted. Existence of IL-1β neutralizing antibody in supernatants recovered the effects (P < 0.0001) of GRIM19 knockdown macrophages on HESC.ConclusionsGRIM19 downregulation induces pyroptosis of macrophages through NLRP3 pathway, increases the secretion of IL-1β and promotes adenomyosis progression.

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Condition tags

adenomyosis

MeSH descriptors

Adenomyosis Adenomyosis Apoptosis Regulatory Proteins NADH, NADPH Oxidoreductases NLR Family, Pyrin Domain-Containing 3 Protein NLR Family, Pyrin Domain-Containing 3 Protein NLR Family, Pyrin Domain-Containing 3 Protein Antibodies, Neutralizing Antibodies, Neutralizing Apoptosis Regulatory Proteins Down-Regulation Female Humans Macrophages Macrophages NADH, NADPH Oxidoreductases Pyroptosis

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