| Project/Area Number |
15390114
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
NAKANUMA Yasuni Graduate School of Medical Science, Professor, 医学系研究科, 教授 (10115256)
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| Co-Investigator(Kenkyū-buntansha) |
SASAKI Motoko Graduate School of Medical Science, Associate Professor, 医学系研究科, 助教授 (70225895)
HARADA Kenichi Graduate School of Medical Science, Assistant Professor, 医学系研究科, 助教授 (30283112)
SATO Yasunori Graduate School of Medical Science, Assistant Professor, 医学系研究科, 講師 (30324073)
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| Project Period (FY) |
2003 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥14,100,000 (Direct Cost: ¥14,100,000)
Fiscal Year 2006: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥4,500,000 (Direct Cost: ¥4,500,000)
Fiscal Year 2003: ¥7,700,000 (Direct Cost: ¥7,700,000)
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| Keywords | primary biliary cirrhosis / culture / innate immunity / microorganism / Toll-like receptor / biliary tract / signal transduction / self defence / フラクタルカイン / 肝内胆管系 / 自然免役 / 細菌感染 / シグナル伝達系 / リポタイコ酸 / トル様レセプタ / リポポリサッカライド |
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| Research Abstract |
We demonstrated the participation of innate immunity in the pathophysiology of biliary tract by using human materials of hepatobiliary tissues and cultured human biliary epithleial cells. The following three data were obtained. (1) Biliary epithelial cells expressed Toll-like receptor (TLR), and they responded to pathogen associated molecular patterns (PAMPs) as a physiological response of innate immunity. This reaction seemed to be involved physiologically in biliary homeostasis against bacterial components contained in bile. By cultural study, it was found that endotoxin tolerance of TLF4 was induced by two step processes, and that IRAK-M is also involved in this process by a negative regulator. (2) It is reported that biliary atresia could be caused by infection of double strand RNA virus. It was found in this study that biliary epithelial cells express TLR3 reacting with double strand RNA, and NF-B and IFN-β is incuded in these cells by exposing to the ligands of TLR3. In addition, TRAIL, a proapoptotic molecule was also induced in this process. In the affected bile ducts of biliary atresia, TLR3 and TRAIL were expressed in biliary epithelial cells. These findings suggested that virus, particularly double strand RNA virus was likely involved in the pathogenesis of biliary atresia, particularly the apoptotic loss of infected biliary epithelial cells. (3) Primary biliary cirrhosis is an autoimmune liver disease and biliary epithelial cells underwent apoptosis, probably resulting from bacterial infection. By examing the apoptotic mechanisms of biliary epithelial cells and innate immunity, it was found that biliary epithelial cells under protein-recessive state, underwent apoptosis by PAMPs stimulation, and HIAP-1 overexpression was important in antiapoptotic effect of biliary epithelial cells due to PAMPs. These studies showed that innate immunity, especially TLR, is involved in the pathophysiology of the biliary tree.
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