biostudies-literatureXian HUniversity of California San DiegoNCRR NIH HHSNIA NIH HHSNIAID NIH HHSNIEHS NIH HHSNCI NIH HHSNINDS NIH HHSNIAMS NIH HHSNIH HHS1463-1477.e11https://www.ebi.ac.uk/biostudies/studies/S-EPMC8189765biostudies-literatureUnknown54(7)Acute respiratory distress syndrome (ARDS), an inflammatory condition with high mortality rates, is common in severe COVID-19, whose risk is reduced by metformin rather than other anti-diabetic medications. Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1β production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS. By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-κB, metformin blocked LPS-induced and ATP-deImmunityMetformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation.PMC8189765P30 AR073761R01 NS095894RF1 AG057409K01 AR077111U54 CA260591K26 OD010945R01 AI072726P30 CA023100P42 ES010337K26 RR026099R01 AI043477Rundberg Nilsson Ade la Torre JCAleman-Muench GRTourtellotte WGKang STrudler DLipton SALuevanos MSanchez-Lopez EArditi MSoroosh PLiu YTeijaro JZhang YChen WXian HGatchalian RLewis GCrother TRKarin MfalseMetformin inhibition of mitochondrial ATP and DNA synthesis abrogates NLRP3 inflammasome activation and pulmonary inflammation.Acute respiratory distress syndrome (ARDS), an inflammatory condition with high mortality rates, is common in severe COVID-19, whose risk is reduced by metformin rather than other anti-diabetic medications. Detecting of inflammasome assembly in post-mortem COVID-19 lungs, we asked whether and how metformin inhibits inflammasome activation while exerting its anti-inflammatory effect. We show that metformin inhibited NLRP3 inflammasome activation and interleukin (IL)-1β production in cultured and alveolar macrophages along with inflammasome-independent IL-6 secretion, thus attenuating lipopolysaccharide (LPS)- and SARS-CoV-2-induced ARDS. By targeting electron transport chain complex 1 and independently of AMP-activated protein kinase (AMPK) or NF-κB, metformin blocked LPS-induced and ATP-de2021-01-01T00:00:00Z2021 Jul2026-05-09T05:05:51.631Z2022-02-11T16:07:23.201ZS-EPMC81897653411596410.1016/j.immuni.2021.05.004