{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T15:10:38Z","timestamp":1782141038698,"version":"3.54.5"},"reference-count":46,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T00:00:00Z","timestamp":1624233600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 106-2314-B-075-071-MY2"],"award-info":[{"award-number":["MOST 106-2314-B-075-071-MY2"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 108-2314-B-075-021"],"award-info":[{"award-number":["MOST 108-2314-B-075-021"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 109-2314-B-075-021"],"award-info":[{"award-number":["MOST 109-2314-B-075-021"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 108-2628-B-075-008"],"award-info":[{"award-number":["MOST 108-2628-B-075-008"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001868","name":"National Science Council","doi-asserted-by":"publisher","award":["MOST 109-2628-B-075 -016"],"award-info":[{"award-number":["MOST 109-2628-B-075 -016"]}],"id":[{"id":"10.13039\/501100001868","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. The therapeutic effects of eritoran, a TLR4 antagonist, in mice with chronic liver injury remained unclear. C57BL\/6 mice were fed a fast-food diet (FFD) or treated with carbon tetrachloride (CCl4) to induce chronic liver injury. Eritoran (10 mg\/kg) or a vehicle was randomly intraperitoneally administered to the FFD-fed mice and the CCl4-injured mice. Primary mouse liver cells were cultured with lipopolysaccharide (LPS) or eritoran. In both FFD and CCl4 mouse models, eritoran significantly reduced serum ALT levels and decreased hepatic inflammatory cell infiltration without altering hepatic steatosis. Additionally, eritoran attenuated liver fibrosis by decreasing hepatic stellate cells (HSCs) activation and the abundance of \u03b1-smooth muscle actin and transforming growth factor-\u03b21. Hepatic TLR4 downstream signaling including MyD88 expression, NF-\u03baB p65 nuclear translocation, p38 and JNK phosphorylation were successfully inhibited by eritoran. In the in vitro study, LPS-induced nuclear translocation of NF-\u03baB in primary HSCs and Kupffer cells was significantly suppressed by eritoran. In conclusion, eritoran attenuated hepatic inflammation and fibrosis by inhibition of the TLR4 signaling pathway in mice with chronic liver injury. Eritoran may serve as a potential drug for chronic liver disease.<\/jats:p>","DOI":"10.3390\/cells10061562","type":"journal-article","created":{"date-parts":[[2021,6,21]],"date-time":"2021-06-21T13:29:58Z","timestamp":1624282198000},"page":"1562","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Eritoran Attenuates Hepatic Inflammation and Fibrosis in Mice with Chronic Liver Injury"],"prefix":"10.3390","volume":"10","author":[{"given":"Yun-Cheng","family":"Hsieh","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kuei-Chuan","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei-Shan","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teh-Ia","family":"Huo","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"},{"name":"Institute of Pharmacology, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5241-5425","authenticated-orcid":false,"given":"Yi-Hsiang","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Chih","family":"Hou","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Chieh","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan"},{"name":"Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 11217, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S38","DOI":"10.1016\/S0168-8278(02)00429-4","article-title":"Liver fibrosis\u2014From bench to bedside","volume":"38","author":"Friedman","year":"2003","journal-title":"J. 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