{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T15:17:37Z","timestamp":1791040657572,"version":"4.1.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":1765,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,11]]},"abstract":"\n \n \n Tumor necrosis factor \u03b1 (TNF\u03b1) has been implicated in a variety of inflammatory diseases, and anti-TNF\u03b1 has been shown to improve therapy when added to standard of care in chronic hepatitis C virus (HCV) infection. In addition, patients with chronic HCV have increased serum levels of TNF\u03b1 and the macrophage-attracting chemokine (C-C motif) ligand 2 (CCL2). A mouse model of chronic HCV with hepatic nonstructural (NS) 3\/4A protein expression mimics the human infection through a reduced response to double-stranded RNA and cleavage of the T cell protein tyrosine phosphatase. The mice also display a resistance to TNF\u03b1<\/jats:bold>\n \n in vivo.\n <\/jats:bold>\n We therefore analyzed the relationship between NS3\/4A and TNF\u03b1. Wild-type and NS3\/4A-transgenic (Tg) mice were treated with TNF\u03b1\/D-galactosamine (D-galN), acting through the TNF receptor 1 on hepatocytes and macrophages, or lipopolysaccharide (LPS)\/D-galN, acting through Toll-like receptor 4 on sinusoidal endothelial cells, macrophages, and dendritic cells. Mice were analyzed for hepatic signaling, liver damage, TNF\u03b1, and CCL2. Similar to HCV-infected humans, NS3\/4A-Tg mice displayed elevated basal levels of TNF\u03b1 and CCL2. Treatment of NS3\/4A-Tg mice with TNF\u03b1\/D-galN or LPS\/D-galN led to increased hepatic nuclear factor kappa B (NF\u03baB) activation, increased TNF\u03b1 and CCL2 levels, decreased apoptosis, and increased hepatocyte regeneration. Importantly, blocking NF\u03baB activation (bortezomib) or administering anti-TNF\u03b1 (infliximab) 4 hours after LPS\/D-galN injection reversed the resistance of NS3\/4A-Tg mice to TNF\u03b1-induced liver injury.<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion:<\/jats:title>\n \n Resistance to TNF\u03b1 seen in NS3\/4A-Tg mice is explained by a hepatoprotective effect of NF\u03baB and TNF\u03b1. Hence, anti-TNF\u03b1 agents block these effects and are antiviral by promoting hepatocyte apoptosis and preventing hepatocyte regeneration. (Hepatology 2010;.)<\/jats:bold>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/hep.23870","type":"journal-article","created":{"date-parts":[[2010,7,29]],"date-time":"2010-07-29T15:15:09Z","timestamp":1280416509000},"page":"1553-1563","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":33,"title":["Anti\u2013Tumor Necrosis Factor \u03b1 Treatment Promotes Apoptosis and Prevents Liver Regeneration in a Transgenic Mouse Model of Chronic Hepatitis C"],"prefix":"10.1097","volume":"52","author":[{"given":"Erwin 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