Innate Immune Response Induces Apoptosis and Regulates Apoptosis-related Molecules in Human Biliary Epithelial Cells

点击翻译按钮获取中文摘要

Biliary epithelial cells possess the essential components of the innate immune system consisting of Toll-like receptors (TLRs) which recognize pathogen-associated molecular patterns (PAMPs) such as lipopolysaccharide (LPS). LPS is known to cause cell injury including apoptosis. We established human intrahepatic biliary epithelial cells (HIBECs) and examined the PAMPs-induced apoptosis in HIBECs. The distinct induction of apoptosis was not found by the treatment with any bacterial PAMPs, but in the condition of an inhibition of NF-KB-dependent protein synthesis, HIBECs undergo apoptosis by PAMPs in the manner of caspase-dependence. In contrast, stimulation with polyinosinic-polycytidylic acid (poly(I:C), a synthetic analog of viral dsRNA) induced the activation of transcription factors (NF-KB and interferon regulatory factor 3) and the production of interferon-β1 (IFN-β1) as potent antiviral responses in HIBECs. Moreover, poly(I:C) up-regulated the expression of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and both poly(I:C) and TRAIL reduced the viability of cultured human HIBECs by enhancing apoptosis. In conclusion, bacterial and viral PAMPs could induce the apoptosis in human biliary epithelial cells as a result of the biliary innate immune response, supporting the notion that biliary innate immunity is directly associated with the pathogenesis of cholangiopathies in biliary diseases such as primary biliary cirrhosis