{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T21:50:58Z","timestamp":1782251458471,"version":"3.54.5"},"reference-count":38,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T00:00:00Z","timestamp":1467936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Homfor"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"DOI":"10.1371\/journal.pone.0158819","type":"journal-article","created":{"date-parts":[[2016,7,8]],"date-time":"2016-07-08T13:58:51Z","timestamp":1467986331000},"page":"e0158819","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["TLR4 Deficiency Protects against Hepatic Fibrosis and Diethylnitrosamine-Induced Pre-Carcinogenic Liver Injury in Fibrotic Liver"],"prefix":"10.1371","volume":"11","author":[{"given":"Susanne Nicole","family":"Weber","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annika","family":"Bohner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dianne H.","family":"Dapito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert F.","family":"Schwabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Lammert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2016,7,8]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.jhep.2011.12.001","article-title":"EASL\u2013EORTC Clinical Practice Guidelines: Management of hepatocellular carcinoma","volume":"56","author":"JF Dufour","year":"2012","journal-title":"J Hepatol"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1016\/j.cld.2008.07.012","article-title":"Genetic Determinants in Hepatic Fibrosis: From Experimental Models to Fibrogenic Gene Signatures in Humans","volume":"12","author":"S Weber","year":"2008","journal-title":"Clin Liver Dis"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1212","DOI":"10.1053\/j.gastro.2012.07.097","article-title":"Genome-wide association study identifies variants associated with progression of liver fibrosis from HCV infection","volume":"143","author":"E Patin","year":"2012","journal-title":"Gastroenterology"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1007\/s00439-013-1294-3","article-title":"Genome-wide scan revealed that polymorphisms in the PNPLA3, SAMM50, and PARVB genes are associated with development and progression of nonalcoholic fatty liver disease in Japan","volume":"132","author":"T Kitamoto","year":"2013","journal-title":"Hum Genet"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"588","DOI":"10.1073\/pnas.95.2.588","article-title":"A family of human receptors structurally related to Drosophila Toll","volume":"95","author":"FL Rock","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/41131","article-title":"A human homologue of the Drosophila Toll protein signals activation of adaptive immunity","volume":"388","author":"R Medzhitov","year":"1997","journal-title":"Nature"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1038\/nature04267","article-title":"Control of B-cell responses by Toll-like receptors","volume":"438","author":"C Pasare","year":"2005","journal-title":"Nature"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1007\/s00109-008-0426-z","article-title":"Toll-like receptors, wound healing, and carcinogenesis","volume":"87","author":"J Kluwe","year":"2009","journal-title":"J Mol Med"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1399","DOI":"10.1182\/blood-2008-07-019307","article-title":"TLRs and innate immunity","volume":"113","author":"BA Beutler","year":"2009","journal-title":"Blood"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"1886","DOI":"10.1053\/j.gastro.2006.01.038","article-title":"Toll-like receptor signaling in the liver","volume":"130","author":"RF Schwabe","year":"2006","journal-title":"Gastroenterology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1002\/hep.22306","article-title":"Toll-like receptors and adaptor molecules in liver disease: Update","volume":"48","author":"E Seki","year":"2008","journal-title":"Hepatology"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/hep.21308","article-title":"Pattern recognition receptors: A contemporary view on liver diseases","volume":"44","author":"G Szabo","year":"2006","journal-title":"Hepatology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1128\/IAI.70.7.3433-3442.2002","article-title":"Role of toll-like receptors in changes in gene expression and NF-kappa B activation in mouse hepatocytes stimulated with lipopolysaccharide","volume":"70","author":"S Liu","year":"2002","journal-title":"Infect Immun"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"932","DOI":"10.1053\/he.2000.5634","article-title":"Kupffer cell activation by lipopolysaccharide in rats: role for lipopolysaccharide binding protein and toll-like receptor 4","volume":"31","author":"GL Su","year":"2000","journal-title":"Hepatology"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1053\/jhep.2003.50182","article-title":"Toll-like receptor 4 mediates inflammatory signaling by bacterial lipopolysaccharide in human hepatic stellate cells","volume":"37","author":"Y-H Paik","year":"2003","journal-title":"Hepatology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1189\/jlb.0604332","article-title":"Development and functional consequences of LPS tolerance in sinusoidal endothelial cells of the liver","volume":"77","author":"A Uhrig","year":"2005","journal-title":"J Leukoc Biol"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"1657","DOI":"10.1097\/01.LAB.0000097190.56734.FE","article-title":"Lipopolysaccharide activates nuclear factor-kappaB through toll-like receptors and related molecules in cultured biliary epithelial cells","volume":"83","author":"K Harada","year":"2003","journal-title":"Lab Investig"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1053\/jhep.2001.25350","article-title":"Toll-like receptor 4 is involved in the mechanism of early alcohol-induced liver injury in mice","volume":"34","author":"T Uesugi","year":"2001","journal-title":"Hepatology"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1016\/j.jhep.2007.04.019","article-title":"Toll-like receptor-4 signaling and Kupffer cells play pivotal roles in the pathogenesis of non-alcoholic steatohepatitis","volume":"47","author":"CA Rivera","year":"2007","journal-title":"J Hepatol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/nm1663","article-title":"TLR4 enhances TGF-\u03b2 signaling and hepatic fibrosis","volume":"13","author":"E Seki","year":"2007","journal-title":"Nat Med"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"504","DOI":"10.1016\/j.ccr.2012.02.007","article-title":"Promotion of hepatocellular carcinoma by the intestinal microbiota and TLR4","volume":"21","author":"DH Dapito","year":"2012","journal-title":"Cancer Cell"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1002\/hep.22697","article-title":"Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of toll-like receptor 4 to hepatic stellate cell responses","volume":"49","author":"J Guo","year":"2009","journal-title":"Hepatology"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000335606","article-title":"Polymorphism of the TLR4 gene reduces the risk of hepatitis C virus-induced hepatocellular carcinoma","volume":"82","author":"J a. Ag\u00fandez","year":"2012","journal-title":"Oncology"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/0092-8674(93)90380-9","article-title":"Homozygous disruption of the murine mdr2 P-glycoprotein gene leads to a complete absence of phospholipid from bile and to liver disease","volume":"75","author":"JJ Smit","year":"1993","journal-title":"Cell"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1053\/j.gastro.2004.04.009","article-title":"Regurgitation of bile acids from leaky bile ducts causes sclerosing cholangitis in Mdr2 (Abcb4) knockout mice","volume":"127","author":"P Fickert","year":"2004","journal-title":"Gastroenterology"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"175","DOI":"10.4254\/wjh.v2.i5.175","article-title":"Innovative immunohistochemistry identifies MMP-9 expressing macrophages at the invasive front of murine HCC","volume":"2","author":"M Roderfeld","year":"2010","journal-title":"World J Hepatol"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1158\/1541-7786.MCR-07-0172","article-title":"Molecular Mechanisms of Liver Carcinogenesis in the Mdr2-Knockout Mice","volume":"5","author":"M Katzenellenbogen","year":"2007","journal-title":"Mol Cancer Res"},{"key":"ref28","first-page":"1237","article-title":"Mice with homozygous disruption of the mdr2 P-glycoprotein gene. A novel animal model for studies of nonsuppurative inflammatory cholangitis and hepatocarcinogenesis","volume":"145","author":"TH Mauad","year":"1994","journal-title":"Am J Pathol"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1002\/hep.26335","article-title":"Interstrain differences in chronic hepatitis and tumor development in a murine model of inflammation-mediated hepatocarcinogenesis","volume":"58","author":"T Potikha","year":"2013","journal-title":"Hepatology"},{"key":"ref30","first-page":"2085","article-title":"Defective LPS Signaling in C3H\/HeJ and C57BL\/10ScCr Mice: Mutations in Tlr4","volume":"282","author":"A Poltorak","year":"1998","journal-title":"Gene. Science"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"5081","DOI":"10.1096\/fj.12-209379","article-title":"The hepatic phosphatidylcholine transporter ABCB4 as modulator of glucose homeostasis","volume":"26","author":"K Hochrath","year":"2012","journal-title":"FASEB J"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1126\/science.1140485","article-title":"Gender disparity in liver cancer due to sex differences in MyD88-dependent IL-6 production","volume":"317","author":"WE Naugler","year":"2007","journal-title":"Science"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"2041","DOI":"10.1053\/gast.2002.37069","article-title":"Genome-wide analysis of hepatic fibrosis in inbred mice identifies the susceptibility locus Hfib1 on chromosome 15","volume":"123","author":"S Hillebrandt","year":"2002","journal-title":"Gastroenterology"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-2697(81)90261-X","article-title":"A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues","volume":"112","author":"IS Jamall","year":"1981","journal-title":"Anal Biochem"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/hep.23845","article-title":"Endotoxin accumulation prevents carcinogen-induced apoptosis and promotes liver tumorigenesis in rodents","volume":"52","author":"L-X Yu","year":"2010","journal-title":"Hepatology"},{"key":"ref36","first-page":"57","article-title":"The Hallmarks of Cancer Review University of California at San Francisco","volume":"100","author":"D Hanahan","year":"2000"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1136\/gut.2009.183749","article-title":"Gut microbes define liver cancer risk in mice exposed to chemical and viral transgenic hepatocarcinogens","volume":"59","author":"JG Fox","year":"2010","journal-title":"Gut"},{"key":"ref38","first-page":"52","article-title":"Distance burning: how gut microbes promote extraintestinal cancers. Gut Microbes","volume":"2","author":"AB Rogers","year":"2011","journal-title":"Taylor & Francis"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0158819","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,10]],"date-time":"2019-09-10T18:46:25Z","timestamp":1568141185000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0158819"}},"subtitle":[],"editor":[{"given":"Matias A","family":"Avila","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2016,7,8]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2016,7,8]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0158819","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,7,8]]}}}