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Effects of bile acids on biliary epithelial cells: proliferation, cytotoxicity, and cytokine secretion.

机译:胆汁酸对胆管上皮细胞的影响:增殖,细胞毒性和细胞因子分泌。

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摘要

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.
机译:已知对肝细胞具有细胞毒性的疏水性胆汁酸在胆汁淤积期间大量保留在肝脏中。因此,我们研究了具有各种疏水性的胆汁酸对胆管上皮细胞的影响。在牛磺去氧胆酸盐(TUDC),牛磺胆酸盐(TC),牛磺去氧胆酸盐(TDC),牛磺去氧胆酸(TCDC)或牛磺胆碱(TLC)的存在下培养胆道上皮细胞。研究了单核细胞趋化蛋白-1(MCP-1)和白细胞介素6(IL-6)的细胞增殖,活力,凋亡和分泌。 TDC增加细胞增殖,而TLC以剂量依赖性方式(50-500 microM)显着降低细胞增殖。在500 microM下,TLC和TCDC显着降低了细胞活力。 TLC,TDC和TCDC在高浓度下诱导细胞凋亡。 TC显着刺激MCP-1和IL-6的分泌。 TUDC对任何参数都没有显着影响。这些发现表明疏水性胆汁酸具有细胞毒性,并诱导胆汁上皮细胞凋亡。此外,TC是人胆汁中的主要胆汁酸,可刺激胆汁淤积性肝病期间发生的炎症和纤维化过程中涉及的细胞因子的分泌。

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