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Increased hepatic expression of TLR<\/jats:styled-content>s, microRNA<\/jats:styled-content>s, and inflammatory mediators is linked to ethanol (EtOH) exposure and to alcoholic liver disease (ALD<\/jats:styled-content>). ALD<\/jats:styled-content> invovles chronic hepatic inflammation that can progress to alcoholic hepatitis (AH<\/jats:styled-content>), a particularly severe form of ALD<\/jats:styled-content>. This study aimed to investigate TLR<\/jats:styled-content>7 expression in patients with different liver disease phenotypes and in mouse liver following alcohol exposure.<\/jats:p><\/jats:sec>Methods<\/jats:title>Hepatic mRNA<\/jats:styled-content> expression was determined by RNA<\/jats:styled-content> sequencing of liver tissue from patients with liver disease or normal liver tissue. Mice were exposed to subchronic EtOH followed by administration of the TLR<\/jats:styled-content>7 agonist imiquimod. Primary human hepatocytes were exposed to EtOH or imiquimod in\u00a0vitro.<\/jats:p><\/jats:sec>Results<\/jats:title>RNA<\/jats:styled-content>seq analysis revealed that hepatic expression of TLR<\/jats:styled-content>7 and let\u20107b microRNA<\/jats:styled-content>, an endogenous TLR<\/jats:styled-content>7 ligand, was significantly increased in AH<\/jats:styled-content> patients. Hepatic expression of TLR<\/jats:styled-content>7 and let\u20107b positively correlated with hepatic IL<\/jats:styled-content>\u20108 mRNA<\/jats:styled-content> expression. In mice, EtOH increased hepatic TLR<\/jats:styled-content>7 mRNA<\/jats:styled-content> expression and enhanced imiquimod\u2010induced expression of the pro\u2010inflammatory mediators TNF<\/jats:styled-content>\u03b1<\/jats:italic>, MCP<\/jats:styled-content>\u20101, and iNOS<\/jats:styled-content>. In vitro, EtOH significantly increased hepatocyte TLR<\/jats:styled-content>7 mRNA<\/jats:styled-content> and the TLR<\/jats:styled-content>7 agonist, imiquimod, induced hepatocyte expression of TNF<\/jats:styled-content>\u03b1<\/jats:italic> and IL<\/jats:styled-content>\u20108 mRNA<\/jats:styled-content>. EtOH also increased the release of let\u20107b in microvesicles from hepatocytes, suggesting that EtOH can increase the expression of both the receptor and its endogenous ligand.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>These studies suggest that increased TLR<\/jats:styled-content>7 signaling caused by increased expression of TLR<\/jats:styled-content>7 and its endogenous ligand let\u20107b may contribute to the enhanced inflammatory response associated with AH<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.13871","type":"journal-article","created":{"date-parts":[[2018,8,13]],"date-time":"2018-08-13T21:58:01Z","timestamp":1534197481000},"page":"2107-2122","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["TLR<\/scp>7\u2010let\u20107 Signaling Contributes to Ethanol\u2010Induced Hepatic Inflammatory Response in Mice and in Alcoholic Hepatitis"],"prefix":"10.1111","volume":"42","author":[{"given":"Veronica L.","family":"Massey","sequence":"first","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Medical School University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Qin","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Medical School University of North Carolina at Chapel Hill Chapel Hill North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joaquin","family":"Cabezas","sequence":"additional","affiliation":[{"name":"Gastroenterology and Hepatology Hospital Marques de Valdecilla Research Institute Valdecilla Santander Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Caballeria","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) CIBER de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Catalonia Spain"},{"name":"Liver Unit Hospital Clinic Barcelona Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pau","family":"Sancho\u2010Bru","sequence":"additional","affiliation":[{"name":"Institut d'Investigacions Biom\u00e8diques August Pi i Sunyer (IDIBAPS) CIBER de Enfermedades Hep\u00e1ticas y Digestivas (CIBERehd) Barcelona Catalonia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Bataller","sequence":"additional","affiliation":[{"name":"Bowles Center for Alcohol Studies University of North Carolina Medical School University of North Carolina at Chapel Hill Chapel Hill North Carolina"},{"name":"Division of Gastroenterology, Hepatology and Nutrition Center for Liver Diseases Pittsburgh Liver Research Center University of Pittsburgh Medical Center (UPMC) Pittsburgh 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