Development of a novel diagnostic method for early detection of chronic liver diseases through the molecular pathological analysis of chronic liver disease models
Grant-in-Aid for Scientific Research (B)
|Allocation Type||Single-year Grants |
|Research Institution||Kanazawa University |
MUKAIDA Naofumi Kanazawa University, Cancer Research Institute, Professor, がん研究所, 教授 (30182067)
|Project Period (FY)
1999 – 2002
Completed (Fiscal Year 2002)
|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)
|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|
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.
Report (5 results)
Research Products (42 results)