Effects of bile acids on biliary epithelial cells: proliferation,cytotoxicity, and cytokine secretion |
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| Authors: | Lamireau Thierry Zoltowska Monica Levy Emile Yousef Ibrahim Rosenbaum Jean Tuchweber Beatriz Desmoulière Alexis |
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| Institution: | 1. Unité de Recherche en Gastroentérologie-Nutrition, Centre de Recherche, Hôpital Sainte-Justine, Côte Sainte Catherine, Montréal, Québec, Canada;2. Groupe de Recherches pour l''Etude du Foie, INSERM E9917, Université Victor Segalen Bordeaux 2, 146 rue Léo Saignat, 33076 Bordeaux, France;3. Département de Nutrition, Université de Montréal, Montréal, Québec, Canada;4. Département de Pharmacologie, Université de Montréal, Montréal, Québec, Canada;1. Laboratory of Liver Diseases, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA;2. Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA;1. Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, China;2. Department of Critical Care Medicine, the First Affiliated Hospital of Nanchang University, Nanchang, China;3. Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi''an Jiaotong University, Xi''an, China;1. Institute of Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Germany;2. DZHK (German Centre for Cardiovascular Research), Partner Site Greifswald, Germany;3. Institute for Community Medicine, University Medicine Greifswald, Germany;4. Institute of Epidemiology, Christian Albrechts University Kiel, Germany;5. Department of Neurology, University Medicine Greifswald, Germany;6. Department of Cardiology, University Medicine Greifswald, Germany;1. Pathology Department, Faculty of Medicine, Mansoura University, Mansoura, Egypt;2. Department of Public Health, National Liver Institute, Menoufia University, Egypt;3. Faculty of Applied Medical Sciences, Taif University, Taif, Saudi Arabia;4. Department of Medical Biochemistry, Faculty of Medicine, Al-Azhar University, Egypt;5. Department of Medical Laboratory Sciences, Taif University, College of Applied Medical Sciences, Taif, Saudi Arabia |
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| 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. |
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