{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T07:23:15Z","timestamp":1787728995367,"version":"build-2784847793"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2008,12,1]],"date-time":"2008-12-01T00:00:00Z","timestamp":1228089600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Bacterial LPS (endotoxin) is implicated in the pathogenesis of acute liver failure and several chronic inflammatory liver diseases. To evaluate the effect of hepatocyte cyclooxygenase (COX)-2 in LPS-induced liver injury, we generated transgenic mice with targeted expression of COX-2 in the liver by using the albumin promoter-enhancer driven vector and the animals produced were subjected to a standard experimental protocol of LPS-induced acute fulminant hepatic failure (i.p. injection of low dose of LPS in combination with d-galactosamine (d-GalN)). The COX-2 transgenic mice exhibited earlier mortality, higher serum aspartate aminotransferase and alanine aminotransferase levels and more prominent liver tissue damage (parenchymal hemorrhage, neutrophilic inflammation, hepatocyte apoptosis, and necrosis) than wild-type mice. Western blot analysis of the liver tissues showed that LPS\/d-GalN treatment for 4 h induced much higher cleavage of poly(ADP-ribose) polymerase, caspase-3, and caspase-9 in COX-2 transgenic mice than in wild-type mice. Increased hepatic expression of JNK-2 in COX-2 transgenic mice suggest that up-regulation of JNK-2 may represent a potential mechanism for COX-2-mediated exacerbation of liver injury. Blocking the prostaglandin receptor, EP1, prevented LPS\/d-GalN-induced liver injury and hepatocyte apoptosis in COX-2 transgenic mice. Accordingly, the mice with genetic ablation of EP1 showed less LPS\/d-GalN-induced liver damage and less hepatocyte apoptosis with prolonged survival when compared with the wild-type mice. These findings demonstrate that COX-2 and its downstream prostaglandin receptor EP1 signaling pathway accelerates LPS-induced liver injury. Therefore, blocking COX-2-EP1 pathway may represent a potential approach for amelioration of LPS-induced liver injury.<\/jats:p>","DOI":"10.4049\/jimmunol.181.11.8027","type":"journal-article","created":{"date-parts":[[2014,4,18]],"date-time":"2014-04-18T23:09:53Z","timestamp":1397862593000},"page":"8027-8035","source":"Crossref","is-referenced-by-count":33,"title":["Transgenic Expression of Cyclooxygenase-2 in Hepatocytes Accelerates Endotoxin-Induced Acute Liver Failure"],"prefix":"10.1093","volume":"181","author":[{"given":"Chang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"},{"name":"Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, Jilin University , Jilin,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyu","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"},{"name":"Department of Biochemistry, College of Medicine, Chungnam National University , Daejeon,","place":["Korea"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie C","family":"DeFrances","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrashekhar R","family":"Gandhi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Pittsburgh School of Medicine , Pittsburgh, PA 15213"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2008,12,1]]},"reference":[{"key":"2025032719405358000_R1","first-page":"138","article-title":"The pathophysiology and treatment of sepsis","volume-title":"N. 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