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• W3184457842 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 <em>in vitro</em>; 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 mechanism of action, the expression levels of the nuclear factor erythroid 2‑related factor 2 (Nrf‑2)/heme oxygenase‑1 (HO‑1) pathway proteins were analyzed by western blotting. Finally, the regulatory effect of DI on autophagy and its association with inflammation was determined by western blotting. The present study demonstrated that DI administration inhibited NLRP3 assembly, LDH release and GSDMD cleavage. Cotreatment of DI with LPS and ATP facilitated the transition from M1 to M2, reduced inflammatory mediator expression and impeded NF‑κB phosphorylation. In addition, DI effectively reduced reactive oxygen species production through the Nrf‑2/HO‑1 pathway. Moreover, DI induced cellular autophagy, whereas inhibition of autophagy with 3‑methyladenine markedly reversed its inhibitory effect on NLRP3‑dependent pyroptosis. Taken together, the present study suggested that DI participated in the Nrf‑2/HO‑1 pathway and served a key role in microglia inflammation and NLRP3 inflammasome‑mediated pyroptosis via induction of autophagy." @default.
• W3184457842 created "2021-08-02" @default.
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• W3184457842 date "2021-07-21" @default.
• W3184457842 modified "2023-10-12" @default.
• W3184457842 title "Dimethyl itaconate inhibits LPS‑induced microglia inflammation and inflammasome‑mediated pyroptosis via inducing autophagy and regulating the Nrf‑2/HO‑1 signaling pathway" @default.
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• W3184457842 doi "https://doi.org/10.3892/mmr.2021.12311" @default.
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