{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:45:19Z","timestamp":1791276319186,"version":"4.1.0"},"reference-count":41,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2006,4,28]],"date-time":"2006-04-28T00:00:00Z","timestamp":1146182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2006,6]]},"abstract":"<jats:p><jats:bold>Abstract: Background: <\/jats:bold> Tissue inhibitor of metalloproteinases (TIMP)\u20101, the most important endogenous inhibitor of matrix metalloproteinases, plays a pivotal role in the pathogenesis of liver fibrosis and may represent an effective therapeutic target in the design of antifibrotic strategies for chronic liver diseases.<\/jats:p><jats:p><jats:bold>Methods: <\/jats:bold> Intraperitoneal application of a single dose of either tumor necrosis factor (TNF)\u2010\u03b1 or interleukin (IL)\u20101\u03b2 in mice led to an enhanced expression of hepatic TIMP\u20101 after 4\u201316\u2003h. Male Sprague\u2013Dawley rats were treated with carbon tetrachloride (CCl<jats:sub>4<\/jats:sub>) in the presence and absence of specific TNF\u2010\u03b1 and IL\u20101\u03b2 inhibitors.<\/jats:p><jats:p><jats:bold>Results: <\/jats:bold> Real\u2010time PCR revealed a significant increase of TIMP\u20101 mRNA in total rat liver 24\u2003h after CCl<jats:sub>4<\/jats:sub> injection. Repetitive injection of both, etanercept and anakinra, before and after CCl<jats:sub>4<\/jats:sub> injection effectively inactivated TNF\u2010\u03b1 and IL\u20101\u03b2. Anticytokine pretreatment reduced the increase of TIMP\u20101 expression after a single CCl<jats:sub>4<\/jats:sub> injection by 50% and 75%, respectively. In contrast to CCl<jats:sub>4<\/jats:sub>\u2010treated rats with and without TNF\u2010\u03b1 blockade, IL\u20101\u03b2 inactivation caused a sevenfold increase in matrix metalloproteinases\u20109 mRNA levels.<\/jats:p><jats:p><jats:bold>Conclusions: <\/jats:bold> In conclusion, TIMP\u20101 expression is up\u2010regulated in the early phase of toxic liver injury by proinflammatory cytokines such as TNF\u2010\u03b1 and IL\u20101\u03b2 in rodents. Pharmacological inactivation of these cytokines significantly reduces TIMP\u20101 gene expression. Our data provide a potential new antifibrotic approach.<\/jats:p>","DOI":"10.1111\/j.1478-3231.2006.01271.x","type":"journal-article","created":{"date-parts":[[2006,4,29]],"date-time":"2006-04-29T04:23:28Z","timestamp":1146284608000},"page":"579-586","source":"Crossref","is-referenced-by-count":34,"title":["Cytokine blockade inhibits hepatic tissue inhibitor of metalloproteinase\u20101 expression and up\u2010regulates matrix metalloproteinase\u20109 in toxic liver injury"],"prefix":"10.1111","volume":"26","author":[{"given":"Martin","family":"Roderfeld","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Geier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph 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