Dimethyl itaconate inhibits LPS‑induced microglia inflammation and inflammasome‑mediated pyroptosis via inducing autophagy and regulating the Nrf‑2/HO‑1 signaling pathway.

ABSTRACT: The endogenous metabolite itaconate and its cell‑permeable derivative dimethyl itaconate (DI) have been identified as anti‑inflammatory regulators of macrophages; however, their contribution to inflammasome‑mediated pyroptosis remains unknown. The present study examined the molecular mechanism of DI on NLR family pyrin domain‑containing 3 (NLRP3) inflammasome assembly and NLRP3 inflammasome‑dependent pyroptosis in microglia. Lipopolysaccharide (LPS) and ATP were used to induce microglia pyroptosis in vitro; this process was confirmed by TUNEL assay, lactate dehydrogenase (LDH) detection and gasdermin D (GSDMD) expression analysis. The regulation of microglia polarization and inflammatory cytokine expression was assessed by immunofluorescence assays and ELISA. To investigate the associated

SUBMITTER: Yang S 

PROVIDER: S-EPMC8335742 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature