{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:49:29Z","timestamp":1787017769184,"version":"build-2736575974"},"reference-count":21,"publisher":"American Physiological Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p>\n                    Although it is clear that bile acid accumulation is the major initiator of fibrosis caused by cholestatic liver disease, endotoxemia is a common side effect. However, the depletion of hepatic macrophages with gadolinium chloride blunts hepatic fibrosis. Because endotoxin is a key activator of hepatic macrophages, this study was designed to test the hypothesis that LPS signaling through CD14 contributes to hepatic fibrosis caused by experimental cholestasis. Wild-type mice and CD14 knockout mice (CD14\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) underwent sham operation or bile duct ligation and were killed 3 wk later. Measures of liver injury, such as focal necrosis, biliary cell proliferation, and inflammatory cell influx, were not significantly different among the strains 3 wk after bile duct ligation. Markers of liver fibrosis such as Sirius red staining, liver hydroxyproline, and \u03b1-smooth muscle actin expression were blunted in CD14\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared with wild-type mice after bile duct ligation. Despite no difference in lymphocyte infiltration, the macrophage\/monocyte activation marker OX42 (CD11b) and the oxidative stress\/lipid peroxidation marker 4-hydroxynonenal were significantly upregulated in wild-type mice after bile duct ligation but not in CD14\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Increased profibrogenic cytokine mRNA expression in the liver after bile duct ligation was significantly blunted in CD14\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice compared with the wild type. The hypothesis that LPS was involved in experimental cholestatic liver fibrosis was tested using mice deficient in LPS-binding protein (LBP\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ). LBP\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice had less liver injury and fibrosis (Siruis red staining and hydroxyproline content) compared with wild-type mice after bile duct ligation. In conclusion, these data demonstrate that endotoxin in a CD14-dependent manner exacerbates hepatic fibrogenesis and macrophage activation to produce oxidants and cytokines after bile duct ligation.\n                  <\/jats:p>","DOI":"10.1152\/ajpgi.00405.2005","type":"journal-article","created":{"date-parts":[[2006,1,26]],"date-time":"2006-01-26T20:33:10Z","timestamp":1138307590000},"page":"G1318-G1328","source":"Crossref","is-referenced-by-count":107,"title":["LPS signaling enhances hepatic fibrogenesis caused by experimental cholestasis in mice"],"prefix":"10.1152","volume":"290","author":[{"given":"Fuyumi","family":"Isayama","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian 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