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Recent studies suggest that like interleukin-10 (IL-10), AIM is involved in alternatively activated (M2) macrophage polarization. We aimed to understand whether and how AIM is involved in IL-10-induced inhibition of inflammasome activation and resolution of inflammation. First, we demonstrated that IL-10 induced increases in mRNA and protein expression of AIM in murine bone marrow-derived macrophages (BMDM). In addition, genetic and pharmacologic inhibition of STAT3 (signal transducer and activator of transcription 3) reduced IL-10-induced AIM expression. We also found that IL-10-induced STAT3 activity enhanced the AIM promoter activity by directly binding the promoter of the AIM gene. Additionally, reduction of LPS\/adenosine triphosphate (ATP)-induced IL-1\u03b2 production and caspase-1 activation by IL-10 was reversed in BMDM from <jats:italic>AIM<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Treatment of BMDM from both wild type (WT) and <jats:italic>IL-10<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice with recombinant AIM showed the inhibitory effects on IL-1\u03b2 and IL-18 production and caspase-1 activation. Endogenous and exogenous AIM inhibited apoptosis-associated speck-like protein containing a caspase activation and recruitment domain (ASC) speck formation. In LPS-induced acute peritonitis, inhibition of IL-1\u03b2 and IL-18 production in peritoneal lavage fluid (PLF) and serum, reduction of caspase-1 activation in peritoneal macrophages, and reduction of numbers of neutrophils and peritoneal macrophages in PLF by administration of IL-10 were not evident in <jats:italic>AIM<\/jats:italic><jats:sup>\u2212\/\u2212<\/jats:sup> mice. Our in vitro and in vivo data reveal a novel role of AIM in the inhibition of inflammasome-mediated caspase-1 activation and IL-1\u03b2 and IL-18 production.<\/jats:p>","DOI":"10.1038\/s41419-020-03332-w","type":"journal-article","created":{"date-parts":[[2021,1,7]],"date-time":"2021-01-07T20:03:40Z","timestamp":1610049820000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Apoptosis inhibitor of macrophage (AIM) contributes to IL-10-induced anti-inflammatory response through inhibition of inflammasome activation"],"prefix":"10.1038","volume":"12","author":[{"given":"Tae-Hyun","family":"Kim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungwon","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minsuk","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Sun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-3712","authenticated-orcid":false,"given":"Jihee Lee","family":"Kang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,1,4]]},"reference":[{"key":"3332_CR1","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1146\/annurev-immunol-031210-101312","volume":"29","author":"W Ouyang","year":"2011","unstructured":"Ouyang, W., Rutz, S., Crellin, N. 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