Innate Immune Response Induces Apoptosis and Regulates Apoptosis-related Molecules in Human Biliary Epithelial Cells
| Project/Area Number |
18590326
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human pathology
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| Research Institution | Kanazawa University |
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Principal Investigator |
HARADA Kenichi Kanazawa University, Graduate School of Medicine, Associate Professor (30283112)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥3,800,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥300,000)
Fiscal Year 2007: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
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| Keywords | cholangiocytes / apoptosis / innate immunity / TLR / primary biliary cirrhosis / biliary atresia / PAMPs / double-stranded RNA / Fas / caspase / NF-κB |
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| Research Abstract |
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
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Report
(3 results)
Research Products
(17 results)
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[Journal Article] Innate immune response to double-stranded RNA in biliary epithelial cells is associated with the pathogenesis of binary atresia2007
Author(s)
Harada, K., Sato, Y., Itatsu, K., Isse, K., Ikeda, H., Yasoshima, M., Zen, Y., Matsui, A., Nakanuma, Y
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Journal Title
Hepatology 27, 46(4)
Pages: 1146-1154
Description
「研究成果報告書概要(欧文)」より
Related Report
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