{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T14:12:01Z","timestamp":1789913521668,"version":"4.0.1"},"reference-count":45,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2019,4,29]],"date-time":"2019-04-29T00:00:00Z","timestamp":1556496000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000027","name":"National Institute on Alcohol Abuse and Alcoholism","doi-asserted-by":"publisher","award":["R01AA022601"],"award-info":[{"award-number":["R01AA022601"]}],"id":[{"id":"10.13039\/100000027","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alcoholism Clin &amp;amp; Exp Res"],"published-print":{"date-parts":[[2019,7]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>One mechanism underlying the development of alcoholic liver disease is overactivation of the innate immune response. Recent investigations indicate that the lysosomal pathway of autophagy down\u2010regulates the inflammatory state of hepatic macrophages, suggesting that macrophage autophagy may regulate innate immunity in alcoholic liver disease. The function of macrophage autophagy in the development of alcoholic liver disease was examined in studies employing mice with a myeloid\u2010specific decrease in autophagy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Littermate control and <jats:italic>Atg5<\/jats:italic><jats:sup><jats:italic>\u0394mye<\/jats:italic><\/jats:sup> mice lacking <jats:italic>Atg5<\/jats:italic>\u2010dependent myeloid autophagy were administered a Lieber\u2013DeCarli control (<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>) or ethanol diet (<jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>) alone or together with lipopolysaccharide (<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>) and examined for the degree of liver injury and inflammation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Knockout mice with decreased macrophage autophagy had equivalent steatosis but increased mortality and liver injury from <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content> alone. Increased liver injury and hepatocyte death also occurred in <jats:italic>Atg5<\/jats:italic><jats:sup><jats:italic>\u0394mye<\/jats:italic><\/jats:sup> mice administered <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content> in association with systemic inflammation as indicated by elevated serum levels of proinflammatory cytokines. Hepatic macrophage and neutrophil infiltration were unaffected by decreased autophagy, but levels of proinflammatory cytokine gene induction were significantly increased in the livers but not adipose tissue of knockout mice treated with <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>. Inflammasome activation was increased in <jats:styled-content style=\"fixed-case\">ED<\/jats:styled-content>\/<jats:styled-content style=\"fixed-case\">LPS<\/jats:styled-content>\u2010treated knockout mice resulting in elevated interleukin (<jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>)\u20101\u03b2 production. Increased <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101\u03b2 promoted alcoholic liver disease as liver injury was decreased by the administration of an <jats:styled-content style=\"fixed-case\">IL<\/jats:styled-content>\u20101 receptor antagonist.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Macrophage autophagy functions to prevent liver injury from alcohol. This protection is mediated in part by down\u2010regulation of inflammasome\u2010dependent and inflammasome\u2010independent hepatic inflammation. Therapies to increase autophagy may be effective in this disease through anti\u2010inflammatory effects on macrophages.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14041","type":"journal-article","created":{"date-parts":[[2019,4,9]],"date-time":"2019-04-09T12:19:50Z","timestamp":1554812390000},"page":"1403-1413","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["Decreased Macrophage Autophagy Promotes Liver Injury and Inflammation from Alcohol"],"prefix":"10.1111","volume":"43","author":[{"given":"Ghulam","family":"Ilyas","sequence":"first","affiliation":[{"name":"Department of Medicine  Division of Digestive Diseases Emory University School of Medicine Atlanta Georgia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Cingolani","sequence":"additional","affiliation":[{"name":"Department of Medicine  Division of Digestive Diseases Emory University School of Medicine Atlanta 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