| Project/Area Number |
16390385
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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 |
Digestive surgery
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| Research Institution | HYOGO COLLEGE OF MEDICINE |
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Principal Investigator |
IIMURO Yuji HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Associate Professor, 医学部, 助教授 (30252018)
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| Co-Investigator(Kenkyū-buntansha) |
FUJIMOTO Jiro HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Professor, 医学部, 教授 (90199373)
IWASAKI Tsuyoshi HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Associate Professor, 医学部, 助教授 (10151721)
TSUTSUI Hiroko HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Professor, 医学部, 教授 (40236914)
IIBOSHI Yasuhiko HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Research Associate, 医学部, 助手 (10340994)
HIRANO Tadamichi HYOGO COLLEGE OF MEDICINE, Faculty of Medicine, Research Associate, 医学部, 助手 (90340968)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥7,500,000 (Direct Cost: ¥7,500,000)
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| Keywords | Toll-like receptor / liver regeneration / MyD88 / innate immunity / NF-κB / SDF-1 / 骨髄移植 / 肝硬変 |
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| Research Abstract |
Toll-like receptors (TLRs) act as innate immune signal sensors and play central roles in host defense. Myeloid differentiation factor (MyD) 88 is a common adaptor molecule required for signaling mediated by TLRs. When the receptors are activated, cells bearing TLRs produce various proinflammatory cytokines in a MyD88-dependent manner. Liver regeneration following partial hepatectomy (PH) requires innate immune responses, particularly interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) production by Kupffer cells, although the recognition and activation processes are still unknown.
We investigated whether TLR/MyD88 signaling is critical for induction of innate immune responses after PH. In Myd88-/- mice after PH, induction of expression of immediate early genes involved in hepatocyte replication and phosphorylation of STAT3 in the liver, and production of TNF-α/IL-6 by and activation of NF-κB in the Kupffer cells were grossly subnormal and were associated with impaired liver regeneration. However, TLR2, 4 and 9, which recognize gram-negative and -positive bacterial products, are not essential for NF-κB activation and IL-6 production after PH, which excludes a possible contribution of TLR2/TLR4 or TLR9 to MyD88-mediated pathways.
In conclusion, the TLR/MyD88 pathway is essential for incidental liver restoration, particularly its early phase.
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