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Interestingly, theUPR<\/jats:styled-content>signature inAH<\/jats:styled-content>patients and in mice following Gao\u2010Binge feeding was biased toward cell death with increased expression of pro\u2010cell death CCAAT\u2013enhancer\u2010binding protein homologous protein (CHOP) and decreased prosurvivalGRP<\/jats:styled-content>78. TheUPR<\/jats:styled-content>and liver injury 6\u00a0hours after binge were prevented both inMif<\/jats:italic>\u2212\/\u2212<\/jats:italic><\/jats:sup>mice and inMIF<\/jats:styled-content>098\u2010treated mice. However, bothMIF<\/jats:styled-content>interventions led to increased liver injury and exacerbated the hepaticUPR<\/jats:styled-content>9\u00a0hours after binge. Induction of upstreamUPR<\/jats:styled-content>signaling and expression ofCHOP<\/jats:styled-content>protein by thapsigargin in alpha mouse liver 12 hepatocytes were blunted by coexposure toMIF<\/jats:styled-content>098, directly connectingMIF<\/jats:styled-content>toUPR<\/jats:styled-content>in hepatocytes.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The current study revealed that, in addition to its cytokine\/chemokine functions,MIF<\/jats:styled-content>is an upstream regulator ofUPR<\/jats:styled-content>in response to EtOH feeding in mice. Importantly, bothMIF<\/jats:styled-content>andUPR<\/jats:styled-content>can either protect or contribute to liver injury, dependent upon the stage or severity of EtOH\u2010induced liver injury.<\/jats:p><\/jats:sec>","DOI":"10.1111\/acer.14065","type":"journal-article","created":{"date-parts":[[2019,4,22]],"date-time":"2019-04-22T12:40:47Z","timestamp":1555936847000},"page":"1439-1451","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Novel Role of Macrophage Migration Inhibitory Factor in Upstream Control of the Unfolded Protein Response After Ethanol Feeding in Mice"],"prefix":"10.1111","volume":"43","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3218-8418","authenticated-orcid":false,"given":"Kyle Lauren","family":"Poulsen","sequence":"first","affiliation":[{"name":"Department of Inflammation and Immunity Center for Liver Disease Research Cleveland Clinic Cleveland 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