1998 Fiscal Year Final Research Report Summary
Molecularbiological study for the role of sinusoidal cells in pathogenesis of liver disease.
| Project/Area Number |
08407016
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
ISHII Hiromasa Keio University, School of Medicine, Professor, 医学部, 教授 (20051500)
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| Co-Investigator(Kenkyū-buntansha) |
HORIE Yoshinori Keio University, School of medicine, Instructor, 医学部, 助手 (70229227)
KUROSE Iwao Keio University, School of medicine, Instructor, 医学部, 助手 (50234604)
YOKOYAMA Hirokazu Keio University, School of medicine, Assistant Prof., 保健管理センター, 講師 (70200920)
KATO Shinzo Keio University, School of medicine, Assistant Prof., 医学部, 講師 (30177448)
MIURA Soichiro Keio University, School of medicine, Ex-Associate Professor, 医学部(平成8,9年分担), 前助教授 (50138012)
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| Project Period (FY) |
1996 – 1998
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| Keywords | Kupffer cells / Sinusoidal cells / Mitochondrion / NO / TNF-alpha / NF-kB / Endotoxin / Alcohol |
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| Research Abstract |
Aim of this study is to investigate the role of sinusoidal cells, especially Kupffer cells, on various experimental liver injuries. Oxidative stress and release of nitric oxide by Kupffer cells analyzed in relation to hepatocyte injury and apoptosis.
The metabolic changes in hepatoma cells co-cultured with isolated rat Kupffer cells were investigated. NO from Kupffer cells induced mitochondrial dysfunction in tumor cells followed by membrane barrier dysfunction in the liver sinusoid. Increased expression of iNOS and iNOS mRNA in the Kupffer cells co-cultured with hepatoma cells was shown. It is also suggested that CD 18/ICAM-1 dependent cell-to-cell interaction with hepatoma cells causes calcium mobilization and oxidative activation of NF-kB , which may lead to the increase production of NO in Kupffer cells. Kupffer cells stimulated by lipopolysaccharides was also shown to release NO and TNF-a, which resulted in mitochondrial injury in hepatocyte.
Experimental model of alcoholic liver damage in perfused liver showed that superoxide anion was released from Kupffer cells into sinusoid by ethanol administration, and lead to damage in sinusoidal endothelial cells. Kupffer cells were shown to metabolize ethanol by cytochrome P450 2E1. After chronic ethanol feeding, LPS elicited microcirculatory disturbance with smaller dose. Expression of adhesion molecules on leukocytes, and adhesion of leukocytes in sinusoid was shown.
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