{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T18:55:15Z","timestamp":1791053715551,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2008,9,1]],"date-time":"2008-09-01T00:00:00Z","timestamp":1220227200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Chronic ethanol (EtOH) abuse results in the development of steatosis, alcoholic hepatitis, and cirrhosis. Augmented TNF-\u03b1 production by macrophages and Kupffer cells and signaling via the p55 TNF receptor have been shown to be critical for these effects of chronic EtOH; however, the molecular mechanisms leading to augmented TNF-\u03b1 production remain unclear. Using cell culture models and in vivo studies we demonstrate that chronic EtOH results in increased TNF-\u03b1 transcription, which is independent of NF-\u03baB. Using reporter assays and chromatin immunoprecipitation we found that this increased transcription is due to increased IRF-3 binding to and transactivation of the TNF promoter. As IRF-3 is downstream from the TLR4 adaptor TIR-domain-containing adapter-inducing IFN-\u03b2 (Trif), we demonstrate that macrophages from Trif\u2212\/\u2212 mice are resistant to this dysregulation of TNF-\u03b1 transcription by EtOH in vitro as well as EtOH-induced steatosis and TNF dysregulation in vivo. These data demonstrate that the Trif\/IRF-3 pathway is a target to ameliorate liver dysfunction associated with chronic EtOH.<\/jats:p>","DOI":"10.4049\/jimmunol.181.5.3049","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T19:32:15Z","timestamp":1397849535000},"page":"3049-3056","source":"Crossref","is-referenced-by-count":102,"title":["TRIF and IRF-3 Binding to the TNF Promoter Results in Macrophage TNF Dysregulation and Steatosis Induced by Chronic Ethanol"],"prefix":"10.1093","volume":"181","author":[{"given":"Xue-Jun","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Bindas","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon D","family":"Piganelli","sequence":"additional","affiliation":[{"name":"Diabetes Institute, Division of Immunogenetics, Department of Pediatrics, Children\u2019s Hospital of Pittsburgh, University of Pittsburgh , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Magill","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Reiser","sequence":"additional","affiliation":[{"name":"Department of Medicine Gene Therapy Program, Louisiana State University School of Medicine , New Orleans, LA 70112"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay K","family":"Kolls","sequence":"additional","affiliation":[{"name":"Department of Pediatrics"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,9,1]]},"reference":[{"key":"2026012806260260300_R1","first-page":"205","article-title":"Alcohol, host defense, and society","volume-title":"Nat. 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