Yang, Su published the artcileDimethyl itaconate inhibits LPS-induced microglia inflammation and inflammasome-mediated pyroptosis via inducing autophagy and regulating the Nrf-2/HO-1 signaling pathway, Recommanded Product: Dimethyl itaconate, the publication is Molecular Medicine Reports (2021), 24(3), 672, database is CAplus and MEDLINE.
The endogenous metabolite itaconate and its cell-permeable derivative di-Me 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 mol. 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 anal. 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.
Molecular Medicine Reports published new progress about 617-52-7. 617-52-7 belongs to esters-buliding-blocks, auxiliary class Alkenyl,Aliphatic hydrocarbon chain,Ester, name is Dimethyl itaconate, and the molecular formula is C23H28N2O4, Recommanded Product: Dimethyl itaconate.
Referemce:
https://en.wikipedia.org/wiki/Ester,
Ester – an overview | ScienceDirect Topics