{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:43:22Z","timestamp":1786977802079,"version":"build-2736575974"},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"9","license":[{"start":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T00:00:00Z","timestamp":1661212800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatol Commun"],"published-print":{"date-parts":[[2022,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Massive inflammation and liver failure are main contributors to the high mortality in alcohol\u2010associated hepatitis (AH). In recent clinical trials, granulocyte colony\u2010stimulating factor (G\u2010CSF) therapy improved liver function and survival in patients with AH. However, the mechanisms of G\u2010CSF\u2010mediated beneficial effects in AH remain elusive. In this study, we evaluated effects of\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    G\u2010CSF administration, using a mouse model of AH. G\u2010CSF treatment significantly reduced liver damage in alcohol\u2010fed mice even though it increased the numbers of liver\u2010infiltrating immune cells, including neutrophils and inflammatory monocytes. Moreover, G\u2010CSF promoted macrophage polarization toward an M2\u2010like phenotype and increased hepatocyte proliferation, which was indicated by an increased Ki67\u2010positive signal colocalized with hepatocyte nuclear factor 4 alpha (HNF\u20104\u03b1) and cyclin D1 expression in hepatocytes. We found that G\u2010CSF increased G\u2010CSF receptor expression and resulted in reduced levels of phosphorylated \u03b2\u2010catenin in hepatocytes. In the presence of an additional pathogen\u2010associated molecule, lipopolysaccharide (LPS), which is significantly increased in the circulation and liver of patients with AH, the G\u2010CSF\u2010induced hepatoprotective effects were abolished in alcohol\u2010fed mice. We still observed increased Ki67\u2010positive signals in alcohol\u2010fed mice following G\u2010CSF treatment; however, Ki67 and HNF\u20104\u03b1 did not colocalize in LPS\u2010challenged mice.\n                    <jats:italic toggle=\"yes\">Conclusion:<\/jats:italic>\n                    G\u2010CSF treatment increases immune cell populations, particularly neutrophil counts, and promotes M2\u2010like macrophage differentiation in the liver. More importantly, G\u2010CSF treatment reduces alcohol\u2010induced liver injury and promotes hepatocyte proliferation in alcohol\u2010fed mice. These data provide new insights into the understanding of mechanisms mediated by G\u2010CSF and its therapeutic effects in AH.\n                  <\/jats:p>","DOI":"10.1002\/hep4.1925","type":"journal-article","created":{"date-parts":[[2022,8,23]],"date-time":"2022-08-23T04:50:00Z","timestamp":1661230200000},"page":"2322-2339","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":22,"title":["Granulocyte colony\u2010stimulating factor attenuates liver damage by M2 macrophage polarization and hepatocyte proliferation in alcoholic hepatitis in mice"],"prefix":"10.1097","volume":"6","author":[{"given":"Yeonhee","family":"Cho","sequence":"first","affiliation":[{"name":"Department of Medicine,University of Massachusetts Medical School,Worcester,Massachusetts,USA"},{"name":"Department of Medicine,Beth Israel Deaconess Medical Center and Harvard Medical 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Medical School,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Morel","sequence":"additional","affiliation":[{"name":"Advanced Pathology Service,Invicro,Boston,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donna","family":"Catalano","sequence":"additional","affiliation":[{"name":"Department of Medicine,University of Massachusetts Medical School,Worcester,Massachusetts,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyongyi","family":"Szabo","sequence":"additional","affiliation":[{"name":"Department of Medicine,Beth Israel Deaconess Medical Center and Harvard Medical 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