Effects of bile acids on biliary epithelial cells: proliferation, cytotoxicity, and cytokine secretion.
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.
Lamireau
Thierry
T
Unité de Recherche en Gastroentérologie-Nutrition, Centre de Recherche, Hôpital Sainte-Justine, Côte Sainte Catherine, Montréal, Québec, Canada.
Zoltowska
Monica
M
Levy
Emile
E
Yousef
Ibrahim
I
Rosenbaum
Jean
J
Tuchweber
Beatriz
B
Desmoulière
Alexis
A
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
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