| Project/Area Number |
11470516
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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 |
Laboratory medicine
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| Research Institution | Kanazawa University |
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Principal Investigator |
MUKAIDA Naofumi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (30182067)
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| Project Period (FY) |
1999 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥14,200,000 (Direct Cost: ¥14,200,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 1999: ¥3,700,000 (Direct Cost: ¥3,700,000)
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| Keywords | interferon (IFN)-γ / liver fibrosis / interleukin (IL)-6 / tumor necrosis factor-α / liver metastasis / hepatoma / chemokine / interleukin (IL)-1 / アセトアミノフェン / 腫瘍壊死因子 / ケモカイン・レセプター / C型肝炎ウィルス / NS5A蛋白 / インターロイキン8 / インターフェロン / dimethylnitrosamine / 遺伝子欠損マウス / C型肝炎ウイルス / 単球走化因子(MCP-1) / PEA3 / AP-1 / 肉芽腫 / 急性肝障害 / 四塩化炭素 / コラーゲン / インターロイキン12 / インターロイキン18 |
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| Research Abstract |
In order to identify an endogenous bioactive substance(s) which are involved in the chronic phases of inflammation in liver, we analyzed several liver dysfunction models in mice from molecular pathological viewpoints.
#1. We proved that interferon (IFN)-γ regulated the production of pro-inflammatory cytokines and the infiltration of inflammatory cells including neutrophils and macrophages, thereby contributing to the development of lipopolysaccharide (LPS)-induced acute liver injury in Propioniobaciterium acnes-primed mice and acetaminophen-induced acute fatal liver dysfunction.
#2. We obtained the evidence to suggest that interleukin (IL)-6 have bifacial roles in carbon tetrachloride-induced chronic liver fibrosis; induction of fibrogenic process and maintenance of the hepatocyte capacity to produce serum proteins such as albumin, by up-regulating the expression of a potent fibrogenic factor, transforming growth factor-β_1 and hepatocyte growth factor, respectively.
#3. We have provided evidence that tumor necrosis factor receptor p55-mediated signals regulated the accumulation of Kupffer and Ito cells, thereby inducing liver fibrosis.
#4. We observed that intrasplenic injection of tumors induced TNF-α expression and subsequent vascular adhesion molecule-1 expression in sinusoidal endothelial cells in liver, thereby inducing liver metastasis.
#5. We observed that CCL3, induced by endogenously produced IL-1, might interact with its specific receptor, CCR1, constitutively expressed on hepatoma cells, in human hepatoma tissues.
We are in the process to analyze the gene expression patterns between wild-type and various types of cytokine-related gene-deficient mice in the above mentioned inflammation models, in order to identify the molecule(s) which is crucially involved in the development of chronic liver inflammation.
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