{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T19:34:25Z","timestamp":1793043265232,"version":"4.5.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T00:00:00Z","timestamp":1707868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AA017729 R01 AA020744 R01 AA011576"],"award-info":[{"award-number":["R01 AA017729 R01 AA020744 R01 AA011576"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Background and aims:<\/jats:bold> Granulocyte colony-stimulating factor (G-CSF) has been proposed as a therapeutic option for patients with ACLF, however clinical outcomes are controversial. We aimed at dissecting the role of G-CSF in an alcohol-induced murine model of ACLF.<\/jats:p><jats:p><jats:bold>Methods<\/jats:bold>: ACLF was triggered by a single alcohol binge (5\u00a0g\/kg) in a bile duct ligation (BDL) liver fibrosis model. A subgroup of mice received two G-CSF (200\u00a0\u03bcg\/kg) or vehicle injections prior to acute decompensation with alcohol. Liver, blood and brain tissues were assessed.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Alcohol binge administered to BDL-fibrotic mice resulted in features of ACLF indicated by a significant increase in liver damage and systemic inflammation compared to BDL alone. G-CSF treatment in ACLF mice induced an increase in liver regeneration and neutrophil infiltration in the liver compared to vehicle-treated ACLF mice. Moreover, liver-infiltrating neutrophils in G-CSF-treated mice exhibited an activated phenotype indicated by increased expression of CXC motif chemokine receptor 2, leukotriene B4 receptor 1, and calprotectin. In the liver, G-CSF triggered increased oxidative stress, type I interferon response, extracellular matrix remodeling and inflammasome activation. Circulating IL-1\u03b2 was also increased after G-CSF treatment. In the cerebellum, G-CSF increased neutrophil infiltration and S100a8\/9 expression, induced microglia proliferation and reactive astrocytes, which was accompanied by oxidative stress, and inflammasome activation compared to vehicle-treated ACLF mice.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> In our novel ACLF model triggered by alcohol binge that mimics ACLF pathophysiology, neutrophil infiltration and S100a8\/9 expression in the liver and brain indicate increased tissue damage, accompanied by oxidative stress and inflammasome activation after G-CSF treatment.<\/jats:p>","DOI":"10.3389\/fcell.2024.1347395","type":"journal-article","created":{"date-parts":[[2024,2,14]],"date-time":"2024-02-14T04:27:15Z","timestamp":1707884835000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["G-CSF increases calprotectin expression, liver damage and neuroinflammation in a murine model of alcohol-induced ACLF"],"prefix":"10.3389","volume":"12","author":[{"given":"Mart\u00ed","family":"Ortega-Ribera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Zhuang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronika","family":"Brezani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prashanth","family":"Thevkar Nagesh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radhika S.","family":"Joshi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mrigya","family":"Babuta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanbo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gyongyi","family":"Szabo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1056\/NEJMra1914900","article-title":"Acute-on-Chronic liver failure","volume":"382","author":"Arroyo","year":"2020","journal-title":"N. 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