{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T22:32:23Z","timestamp":1790980343275,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2007,5,14]],"date-time":"2007-05-14T00:00:00Z","timestamp":1179100800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2007,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p><jats:bold>Background and Aim:\u2002<\/jats:bold> It has recently been reported that Toll\u2010like receptor 4 (TLR4) is involved in cellular responses to lipopolysaccharides (LPS) and early liver injury induced by LPS. The aim of the present study was to investigate the alterations of <jats:italic>TLR4<\/jats:italic> gene expression in liver tissues and Kupffer cells during the course of carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>)\u2010induced chronic liver injury and fibrosis and its role in liver injury.<\/jats:p><jats:p><jats:bold>Methods:\u2002<\/jats:bold> Rats were induced with liver injury and fibrosis by CCl<jats:sub>4<\/jats:sub> administered subcutaneously twice weekly for up to 8\u2003weeks. The Kupffer cells were isolated by the combined collagenase\u2013pronase perfusion method and incubated with varying doses of LPS. The mRNA expression of TLR4 in liver tissues and Kupffer cells was measured by reverse transcriptase polymerase chain reaction. The levels of tumor necrosis factor (TNF)\u2010\u03b1 in Kupffer cell culture supernatants were determined by enzyme\u2010linked immunosorbent assay. The plasma levels of the endotoxin were determined by chromogenic substrate limulus amebocyte lysate assay. The association of the endotoxin receptor expression with plasma endotoxin levels was assessed.<\/jats:p><jats:p><jats:bold>Results:\u2002<\/jats:bold> CCl<jats:sub>4<\/jats:sub> administration elicited extensive changes in liver morphology, including steatosis, inflammation, necrosis, and fibrosis. Low levels of TLR4 mRNA were detected in normal rat liver tissues, but no expression was detected in the Kupffer cells. The expression of TLR4 mRNA in liver tissues and Kupffer cells was increased 2\u2003weeks after CCl<jats:sub>4<\/jats:sub> administration, peaked at 4 and 6\u2003weeks, and declined at 8\u2003weeks. Basic TNF\u2010\u03b1 production of Kupffer cells isolated from CCl<jats:sub>4<\/jats:sub>\u2010treated rats at 4 and 6\u2003weeks was significantly higher than that of normal rats (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.05). Upon LPS stimulation, production of TNF\u2010\u03b1 was markedly increased in Kupffer cells isolated from normal and 2\u2010,4\u2010, and 6\u2010week CCl<jats:sub>4<\/jats:sub>\u2010treated rats. Moreover, LPS\u2010induced TNF\u2010\u03b1 production was dose\u2010dependent. The plasma levels of the endotoxin were increased during the time of liver injury. There was a correlation between plasma endotoxin levels and <jats:italic>TLR4<\/jats:italic> gene expression in the early and middle stage of liver injury.<\/jats:p><jats:p><jats:bold>Conclusion:\u2002<\/jats:bold> The gene expression of <jats:italic>TLR4<\/jats:italic> was upregulated during the course of CCl<jats:sub>4<\/jats:sub>\u2010induced liver injury, which is associated with the degree of liver injury and Kupffer cell activation. The gut\u2010derived endotoxin may be involved in the upregulation of TLR4 expression.<\/jats:p>","DOI":"10.1111\/j.1440-1746.2007.04896.x","type":"journal-article","created":{"date-parts":[[2007,5,15]],"date-time":"2007-05-15T07:38:10Z","timestamp":1179214690000},"page":"862-869","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Expression of Toll\u2010like receptor 4 in rat liver during the course of carbon tetrachloride\u2010induced liver injury"],"prefix":"10.1111","volume":"22","author":[{"given":"Jing","family":"Hua","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"De Kai","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Qiang","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eng 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