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In this study, we found that ACA suppressed NLRP3 inflammasome activation in mouse bone marrow-derived macrophages and human THP-1 monocytes. ACA inhibited Caspase-1 activation and IL-1\u03b2 production by NLRP3 agonists such as nigericin, monosodium urate (MSU) crystals, and ATP. Moreover, it suppressed oligomerization of the adapter molecule, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1-mediated cleavage of pyroptosis executor Gasdermin D. Mechanistically, ACA inhibited generation of mitochondrial reactive oxygen species (ROS) and prevented release of oxidized mitochondrial DNA, which trigger NLRP3 inflammasome activation. ACA also prevented NLRP3 inflammasome activation in vivo, as evidenced in the MSU crystal-induced peritonitis and dextran sodium sulfate-induced colitis mouse models accompanied by decreased Caspase-1 activation. Thus, ACA is a potent inhibitor of the NLRP3 inflammasome for prevention of NLRP3-associated inflammatory diseases.<\/jats:p>","DOI":"10.1093\/intimm\/dxab016","type":"journal-article","created":{"date-parts":[[2021,4,6]],"date-time":"2021-04-06T11:20:56Z","timestamp":1617708056000},"page":"373-386","source":"Crossref","is-referenced-by-count":30,"title":["1\u2032-Acetoxychavicol acetate inhibits NLRP3-dependent inflammasome activation via mitochondrial ROS suppression"],"prefix":"10.1093","volume":"33","author":[{"given":"Sophia P M","family":"Sok","sequence":"first","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"},{"name":"Institute of Biological Sciences (Genetics and Molecular Biology), Faculty of Science, University of Malaya , Kuala Lumpur 50603 , Malaysia"},{"name":"Centre of Research in Biotechnology for Agriculture (CEBAR), University of Malaya , Kuala Lumpur 50603 , Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daisuke","family":"Ori","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayana","family":"Wada","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruna","family":"Okude","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Kawasaki","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masatoshi","family":"Momota","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noor Hasima","family":"Nagoor","sequence":"additional","affiliation":[{"name":"Institute of Biological Sciences (Genetics and Molecular Biology), Faculty of Science, University of Malaya , Kuala Lumpur 50603 , Malaysia"},{"name":"Centre of Research in Biotechnology for Agriculture (CEBAR), University of Malaya , Kuala Lumpur 50603 , Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taro","family":"Kawai","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Immunobiology, Division of Biological Science, Graduate School of Science and Technology, Nara Institute of Science and Technology (NAIST) , Nara 630-0192 , Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,4,8]]},"reference":[{"key":"2022070116464649700_CIT0001","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1093\/intimm\/dxp017","article-title":"The roles of TLRs, RLRs and NLRs in pathogen recognition","volume":"21","author":"Kawai","year":"2009","journal-title":"Int. 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