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Much of the current literature on cholestatic liver injury is derived from <jats:italic>in\u00a0vitro<\/jats:italic> studies using rodent hepatocytes or cell lines transfected with bile acid (<jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>) uptake transporters. While these studies demonstrate <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content>\u2010driven apoptosis, it is debatable whether these models reflect the human pathophysiology, as primary human hepatocytes undergo primarily necrosis. Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells are a bipotential, human hepatoma line that express apical and basolateral <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> transporters. Thus, we sought to determine whether Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells could replicate the response of primary human hepatocytes to <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> exposure <jats:italic>in\u00a0vitro<\/jats:italic>. HepG2 cells, primary murine hepatocytes (<jats:styled-content style=\"fixed-case\">PMH<\/jats:styled-content>) or Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells, were exposed to taurocholic acid (<jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content>), or glycochenodeoxycholate (<jats:styled-content style=\"fixed-case\">GCDC<\/jats:styled-content>) and lactate dehydrogenase release were measured to determine cell death. Cell death occurred dose\u2010responsively in Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells when exposed to <jats:styled-content style=\"fixed-case\">GCDC<\/jats:styled-content>; however, HepG2 cells died acutely only at very high concentrations of <jats:styled-content style=\"fixed-case\">GCDC<\/jats:styled-content>. In Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells, pre\u2010treatment with the caspase inhibitor z\u2010<jats:styled-content style=\"fixed-case\">VD<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">FMK<\/jats:styled-content> had no effect on cell death, indicating a lack of apoptotic cell death, and while c\u2010jun N\u2010terminal kinase (<jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content>) protein was activated by <jats:styled-content style=\"fixed-case\">GCDC<\/jats:styled-content> treatment in Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells, the inhibition of <jats:styled-content style=\"fixed-case\">JNK<\/jats:styled-content> did not protect. Although previous data indicate that <jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content> stimulates pro\u2010inflammatory gene induction in <jats:styled-content style=\"fixed-case\">PMH<\/jats:styled-content>, there was no change in gene expression after <jats:styled-content style=\"fixed-case\">TCA<\/jats:styled-content> stimulation in Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells, which mimicked previous data found in primary human hepatocytes. These data provide evidence for Hepa<jats:styled-content style=\"fixed-case\">RG<\/jats:styled-content> cells as a new model for the study of the effect of <jats:styled-content style=\"fixed-case\">BA<\/jats:styled-content> on human hepatocytes.<\/jats:p>","DOI":"10.1111\/bcpt.12449","type":"journal-article","created":{"date-parts":[[2015,7,14]],"date-time":"2015-07-14T23:12:41Z","timestamp":1436915561000},"page":"160-167","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Bile Acid\u2010Induced Toxicity in Hepa<scp>RG<\/scp> Cells Recapitulates the Response in Primary Human Hepatocytes"],"prefix":"10.1111","volume":"118","author":[{"given":"Benjamin L.","family":"Woolbright","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitchell R.","family":"McGill","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huimin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Jaeschke","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Therapeutics University of Kansas Medical Center Kansas City KS USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,8,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v18.i36.4985"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116546"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI117579"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.1997.v113.pm9352877"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M804585200"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1067\/msy.2003.237"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2015.01.015"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02662.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0022094"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajpath.2010.11.026"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2004.01.002"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2006.12.003"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24132"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.024"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840180523"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfh151"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.160.7.3480"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2014.04.001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.014"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510230518"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0059432"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27165"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfu122"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2014.05.010"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840120307"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfv041"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1746.2006.04646.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M708916200"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2010.04.015"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.90435.2008"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOG.0b013e328352aab2"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl\u20102014\u2010308410"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2003.50472"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1053\/gast.2002.35948"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2013.10.030"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2353\/ajpath.2007.061133"}],"container-title":["Basic &amp; 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