{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:13:30Z","timestamp":1785150810428,"version":"3.55.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T00:00:00Z","timestamp":1532649600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"DOI":"10.3389\/fimmu.2018.01735","type":"journal-article","created":{"date-parts":[[2018,7,27]],"date-time":"2018-07-27T04:18:11Z","timestamp":1532665091000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["\u03b2-Defensin 1 Is Prominent in the Liver and Induced During Cholestasis by Bilirubin and Bile Acids via Farnesoid X Receptor and Constitutive Androstane Receptor"],"prefix":"10.3389","volume":"9","author":[{"given":"Thomas","family":"Klag","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Thomas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Ehmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lioba","family":"Courth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Mail\u00e4nder-Sanchez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas S.","family":"Weiss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rania","family":"Dayoub","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerstin","family":"Abshagen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Vollmar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wolfgang E.","family":"Thasler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduard F.","family":"Stange","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph P.","family":"Berg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisar P.","family":"Malek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich M.","family":"Zanger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Wehkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,7,27]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jcmgh.2015.04.003","article-title":"The gut microbiota and liver disease","volume":"1","author":"Llorente","year":"2015","journal-title":"Cell Mol Gastroenterol Hepatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1002\/hep.26695","article-title":"Dysbiosis contributes to fibrogenesis in the course of chronic liver injury in mice","volume":"59","author":"De Minicis","year":"2014","journal-title":"Hepatology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1113\/jphysiol.2011.219691","article-title":"Role of innate immunity and the microbiota in liver fibrosis: crosstalk between the liver and the gut","volume":"590","author":"Seki","year":"2012","journal-title":"J Physiol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"706","DOI":"10.1016\/j.jhep.2014.04.015","article-title":"Bacterial translocation in liver cirrhosis: site and role in fibrogenesis","volume":"61","author":"Matuchansky","year":"2014","journal-title":"J Hepatol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1154","DOI":"10.1002\/hep.24789","article-title":"Intestinal bacterial translocation in rats with cirrhosis is related to compromised Paneth cell antimicrobial host defense","volume":"55","author":"Teltschik","year":"2012","journal-title":"Hepatology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/1471-230X-14-40","article-title":"Changes in gut bacterial populations and their translocation into liver and ascites in alcoholic liver cirrhotics","volume":"14","author":"Tuomisto","year":"2014","journal-title":"BMC Gastroenterol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.jhep.2013.07.044","article-title":"Pathological bacterial translocation in liver cirrhosis","volume":"60","author":"Wiest","year":"2014","journal-title":"J Hepatol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1002\/emmm.201201773","article-title":"Antimicrobial peptides and gut microbiota in homeostasis and pathology","volume":"5","author":"Ostaff","year":"2013","journal-title":"EMBO Mol Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"8772","DOI":"10.1073\/pnas.0905745107","article-title":"Peroxisome proliferator-activated receptor gamma activation is required for maintenance of innate antimicrobial immunity in the colon","volume":"107","author":"Peyrin-Biroulet","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1038\/mi.2013.17","article-title":"Cell-mediated reduction of human b-defensin 1: a major role for mucosal thioredoxin","volume":"6","author":"Jaeger","year":"2013","journal-title":"Mucosal Immunol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"419","DOI":"10.1038\/nature09674","article-title":"Reduction of disulphide bonds unmasks potent antimicrobial activity of human b-defensin 1","volume":"469","author":"Schroeder","year":"2011","journal-title":"Nature"},{"key":"B12","doi-asserted-by":"publisher","first-page":"14000","DOI":"10.1073\/pnas.1510084112","article-title":"Crohn\u2019s disease-derived monocytes fail to induce Paneth cell defensins","volume":"112","author":"Courth","year":"2015","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B13","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1159\/000431071","article-title":"Biliary mucosal barrier and microbiome","volume":"31","author":"Verdier","year":"2015","journal-title":"Viszeralmedizin"},{"key":"B14","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1186\/1471-2164-14-669","article-title":"Gut microbiota dysbiosis and bacterial community assembly associated with cholesterol gallstones in largescale study","volume":"14","author":"Wu","year":"2013","journal-title":"BMC Genomics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1007\/BF01296423","article-title":"Defense system in the biliary tract against bacterial infection","volume":"37","author":"Sung","year":"1992","journal-title":"Dig Dis Sci"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.1053\/j.gastro.2008.12.040","article-title":"Bile salts control the antimicrobial peptide cathelicidin through nuclear receptors in the human biliary epithelium","volume":"136","author":"D\u2019Aldebert","year":"2009","journal-title":"Gastroenterology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e16454","DOI":"10.1371\/journal.pone.0016454","article-title":"Hepcidin is an antibacterial, stress-inducible peptide of the biliary system","volume":"6","author":"Strnad","year":"2011","journal-title":"PLoS One"},{"key":"B18","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1002\/hep.1840400423","article-title":"Peptide antibiotic human beta-defensin-1 and -2 contribute to antimicrobial defense of the intrahepatic biliary tree","volume":"40","author":"Harada","year":"2004","journal-title":"Hepatology"},{"key":"B19","doi-asserted-by":"publisher","first-page":"373878","DOI":"10.1155\/2010\/373878","article-title":"Biliary innate immunity: function and modulation","volume":"2010","author":"Harada","year":"2010","journal-title":"Mediators Inflamm"},{"key":"B20","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1067\/mic.2000.107071","article-title":"Bacteriology and antimicrobial choice in hepatolithiasis","volume":"28","author":"Sheen-Chen","year":"2000","journal-title":"Am J Infect Control"},{"key":"B21","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/tpj.2011.44","article-title":"Genomics of ADME gene expression: mapping expression quantitative trait loci relevant for absorption, distribution, metabolism and excretion of drugs in human liver","volume":"13","author":"Schr\u00f6der","year":"2013","journal-title":"Pharmacogenomics J"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1227","DOI":"10.1002\/hep.23103","article-title":"Expression of organic cation transporters OCT1 (SLC22A1) and OCT3 (SLC22A3) is affected by genetic factors and cholestasis in human liver","volume":"50","author":"Nies","year":"2009","journal-title":"Hepatology"},{"key":"B23","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12918-015-0229-0","article-title":"Pathobiochemical signatures of cholestatic liver diseases in bile duct ligated mice","volume":"9","author":"Abshagen","year":"2015","journal-title":"BMC Syst Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1038\/ni797","article-title":"Paneth cell trypsin is the processing enzyme for human defensin-5","volume":"3","author":"Ghosh","year":"2002","journal-title":"Nat Immunol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1124\/dmd.114.060962","article-title":"A systematic comparison of the impact of inflammatory signaling on ADME gene expression and activity in primary human hepatocytes and HepaRG cells","volume":"43","author":"Klein","year":"2015","journal-title":"Drug Metab Dispos"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1124\/dmd.115.064667","article-title":"Comparative analysis and functional characterization of HC-AFW1 hepatocarcinoma cells: CYP expression and induction by nuclear receptor agonists","volume":"43","author":"Braeuning","year":"2015","journal-title":"Drug Metab Dispos"},{"key":"B27","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.4049\/jimmunol.174.6.3709","article-title":"Unconjugated bilirubin inhibits VCAM-1-mediated transendothelial leukocyte migration","volume":"174","author":"Keshavan","year":"2005","journal-title":"J Immunol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1124\/mol.112.082503","article-title":"Direct transcriptional regulation of human hepatic cytochrome P450 3A4 (CYP3A4) by peroxisome proliferator-activated receptor alpha (PPAR\u03b1)","volume":"83","author":"Thomas","year":"2013","journal-title":"Mol Pharmacol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1186\/s12885-015-1500-x","article-title":"The truncated splice variant of peroxisome proliferator-activated receptor alpha, PPAR\u03b1-tr, autonomously regulates proliferative and pro-inflammatory genes","volume":"15","author":"Thomas","year":"2015","journal-title":"BMC Cancer"},{"key":"B30","doi-asserted-by":"publisher","first-page":"261","DOI":"10.3389\/fphar.2015.00261","article-title":"Peroxisome proliferator-activated receptor alpha, PPAR\u03b1, directly regulates transcription of cytochrome P450 CYP2C8","volume":"6","author":"Thomas","year":"2015","journal-title":"Front Pharm"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2003","DOI":"10.1159\/000362976","article-title":"Targeting nuclear receptors with lentivirus-delivered small RNAs in primary human hepatocytes","volume":"33","author":"Thomas","year":"2014","journal-title":"Cell Physiol Biochem"},{"key":"B32","doi-asserted-by":"publisher","first-page":"579","DOI":"10.2217\/pgs.09.7","article-title":"Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation","volume":"10","author":"Gomes","year":"2009","journal-title":"Pharmacogenomics"},{"key":"B33","doi-asserted-by":"publisher","first-page":"e0135852","DOI":"10.1371\/journal.pone.0135852","article-title":"LEMming: a tool for analysis of parallel quantitative real-time PCR measurements independent from reference genes","volume":"10","author":"Feuer","year":"2015","journal-title":"PLoS One"},{"key":"B34","doi-asserted-by":"crossref","first-page":"3542","DOI":"10.1128\/IAI.67.7.3542-3547.1999","article-title":"Mouse beta-defensin 3 is an inducible antimicrobial peptide expressed in the epithelia of multiple organs","volume":"67","author":"Bals","year":"1999","journal-title":"Infect Immun"},{"key":"B35","doi-asserted-by":"publisher","first-page":"4156","DOI":"10.1073\/pnas.0630614100","article-title":"Induction of bilirubin clearance by the constitutive androstane receptor (CAR)","volume":"100","author":"Huang","year":"2003","journal-title":"Proc Natl Acad Sci U S A"},{"key":"B36","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1016\/0009-8981(96)06305-X","article-title":"Hepatic levels of bile acids in end-stage chronic cholestatic liver disease","volume":"251","author":"Fischer","year":"1996","journal-title":"Clin Chim Acta"},{"key":"B37","doi-asserted-by":"publisher","first-page":"571","DOI":"10.1053\/bega.2000.0104","article-title":"The pathophysiology of cholestasis with special reference to primary biliary cirrhosis","volume":"14","author":"Jansen","year":"2000","journal-title":"Baillieres Clin Gastroenterol"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1007\/s00204-015-1522-9","article-title":"Regulation of gene expression by CAR: an update","volume":"89","author":"Kobayashi","year":"2015","journal-title":"Arch Toxicol"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1016\/j.bbagrm.2016.03.007","article-title":"Genomewide comparison of the inducible transcriptomes of nuclear receptors CAR, PXR and PPAR\u03b1 in primary human hepatocytes","volume":"1859","author":"Kandel","year":"2016","journal-title":"Biochim Biophys Acta"},{"key":"B40","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1002\/hep.27744","article-title":"On fibrates and cholestasis: a review","volume":"62","author":"Ghonem","year":"2015","journal-title":"Hepatology"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1678","DOI":"10.1172\/JCI18945","article-title":"Hepatoprotection by the farnesoid X receptor agonist SW 4064 in rat models of intra- and extrahepatic cholestasis","volume":"112","author":"Liu","year":"2003","journal-title":"J Clin Inv"},{"key":"B42","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1159\/000445268","article-title":"Farnesoid X receptor agonists and other bile acids signaling strategies for treatment of liver disease","volume":"34","author":"Halilbasic","year":"2016","journal-title":"Dig Dis"},{"key":"B43","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1186\/1471-230X-7-44","article-title":"Peroxisome proliferators-activated alpha agonist treatment ameliorates hepatic damage in rats with obstructive jaundice: an experimental study","volume":"7","author":"Cindoruk","year":"2007","journal-title":"BMC Gastroenterol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1053\/j.gastro.2014.12.005","article-title":"Efficacy of obeticholic acid in patients with primary biliary cirrhosis and inadequate response to ursodesoxycholic acid","volume":"148","author":"Hirschfield","year":"2015","journal-title":"Gastroenterology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"631","DOI":"10.1056\/NEJMoa1509840","article-title":"A placebo-controlled trial of obeticholic acid in primary biliary cholangitis","volume":"375","author":"Nevens","year":"2016","journal-title":"N Engl J Med"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1007\/s40265-016-0616-x","article-title":"Obeticholic acid: first global approval","volume":"76","author":"Markham","year":"2016","journal-title":"Drugs"},{"key":"B47","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1159\/000368304","article-title":"The anti-microbial peptide LL-37\/CRAMP is elevated in patients with liver diseases and acts as a protective factor during mouse liver injury","volume":"91","author":"Wertenbruch","year":"2015","journal-title":"Digestion"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01735\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,6]],"date-time":"2020-11-06T20:50:19Z","timestamp":1604695819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fimmu.2018.01735\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,27]]},"references-count":47,"alternative-id":["10.3389\/fimmu.2018.01735"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2018.01735","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,27]]},"article-number":"1735"}}