1995 Fiscal Year Final Research Report Summary
Investigation for induction of apoptosis-related genes in hepatitis C virus-infected hepatocytes.
| Project/Area Number |
06670544
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Gastroenterology
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| Research Institution | Osaka University |
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Principal Investigator |
FUSAMOTO Hideyuki Osaka University, Medical School, Associate Professor, 医学部, 助教授 (90124776)
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| Co-Investigator(Kenkyū-buntansha) |
MITA Eiji Osaka University, Medical School, Medical Stuff, 医学部附属病院, 医員
SASAKI Yutaka Osaka University, Medical School, Assistant Professor, 医学部, 助手 (70235282)
KASAHARA Akinori Osaka University, Medical School, Assistant Professor, 医学部, 助手 (70214286)
HAYASHI Norio Osaka University, Medical School, Associate Professor, 医学部, 講師 (00144478)
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| Project Period (FY) |
1994 – 1995
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| Keywords | Fas antigen / Human Fas ligand / Apoptosis / Chronic hepatitis C / Hepatitis C virus / Humanleukocyte Antigen / Cytotoxic T cell / Natural killer cell |
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| Research Abstract |
Apoptosis is a programd cell death that is involved in pathogenesis and progression in various diseases. Fas, which belongs to a TNF/NGF receptor family, leads its expressing cells to apoptosis after being bound to soluble-or membrane-bound Fas ligand. We have already demonstrated that Fas antigen is expressed in hepatocytes obtained from patients with chronic hepatitis C and the degree of Fas expression is correlated with severity of liver inflammation. Furthermore, Fas-expressing hepatocytes were adjacent to or nearly identical with HCV-core antigen expressing cells, implying that HCV induces Fas antigen on infected hepatocytes. To explore the role of Fas-mediated apoptosis in HCV-infection, we examined whether Fas-ligand is expressed in liver-infiltrating lymphocytes and peripheral blood lymphocytes. We have cloned and sequenced human Fas-ligand cDNA based on PCR amplification technique. Monoclonal anti-human Fas-ligand antibody was obtained from mice immunized with Fas-ligand protein. Fas-ligand was strongly expressed on liver-infiltrating lymphocytes having CD8+or CD16+ phenotypes. These results indicated that Fas ligand-positive cytotoxic T-cells and/or natural killer cells infiltrate into liver and induce apoptosis in Fas-positive HCV-infected hepatocytes.
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