title: Effects of bile acids on biliary epithelial cells: proliferation, cytotoxicity, and cytokine secretion.
abstract: Hydrophobic bile acids, which are known to be cytotoxic for hepatocytes, are retained in high amount in the liver during cholestasis. Thus, we have investigated the effects of bile acids with various hydrophobicities on biliary epithelial cells. Biliary epithelial cells were cultured in the presence of tauroursodeoxycholate (TUDC), taurocholate (TC), taurodeoxycholate (TDC), taurochenodeoxycholate (TCDC), or taurolithocholate (TLC). Cell proliferation, viability, apoptosis and secretion of monocyte chemotactic protein-1 (MCP-1) and of interleukin-6 (IL-6) were studied. Cell proliferation was increased by TDC, and markedly decreased by TLC in a dose dependent manner (50-500 microM). Cell viability was significantly decreased by TLC and TCDC at 500 microM. TLC, TDC and TCDC induced apoptosis at high concentrations. The secretion of MCP-1 and IL-6 was markedly stimulated by TC. TUDC had no significant effect on any parameter. These findings demonstrate that hydrophobic bile acids were cytotoxic and induced apoptosis of biliary epithelial cells. Furthermore, TC, a major biliary acid in human bile, stimulated secretion of cytokines involved in the inflammatory and fibrotic processes occurring during cholestatic liver diseases.
authors.affiliation: Unité de Recherche en Gastroentérologie-Nutrition, Centre de Recherche, Hôpital Sainte-Justine, Côte Sainte Catherine, Montréal, Québec, Canada.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lamireau
authors.forename: Monica
authors.initials: M
authors.lastname: Zoltowska
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Yousef
authors.forename: Jean
authors.initials: J
authors.lastname: Rosenbaum
authors.forename: Beatriz
authors.initials: B
authors.lastname: Tuchweber
authors.forename: Alexis
authors.initials: A
authors.lastname: Desmoulière
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001647:Bile Acids and Salts / Q000494:pharmacology*; D001652:Bile Ducts / Q000166:cytology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D018932:Chemokine CCL2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004847:Epithelial Cells / Q000187:drug effects; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology; D013656:Taurocholic Acid / Q000494:pharmacology; D013657:Taurodeoxycholic Acid / Q000494:pharmacology; D013658:Taurolithocholic Acid / Q000494:pharmacology
chemical_list: D001647:Bile Acids and Salts; D018932:Chemokine CCL2; D016207:Cytokines; D015850:Interleukin-6; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; D013658:Taurolithocholic Acid; D013656:Taurocholic Acid; C031655:ursodoxicoltaurine