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Investigation for induction of apoptosis-related genes in hepatitis C virus-infected hepatocytes.

Research Project

Project/Area Number 06670544
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionOsaka University

Principal Investigator

FUSAMOTO Hideyuki  Osaka University, Medical School, Associate Professor, 医学部, 助教授 (90124776)

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)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsFas antigen / Human Fas ligand / Apoptosis / Chronic hepatitis C / Hepatitis C virus / Humanleukocyte Antigen / Cytotoxic T cell / Natural killer cell / Fas抗原 / ヒトFasリガンド / RT-PCR / C型肝炎ウイルス / ラットFasリガンド / クローニング
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.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (32 results)

All Other

All Publications (32 results)

  • [Publications] Kanto T.,et al.: "Density analysis of hepatitis C virus particle population in the circulation of infected hosts : Implications for virus neutralization or persistence." J Hepatol. 22. 440-448 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T.,et al.: "Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alfa." J Med Virol. 46. 230-237 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki N.,et al.: "The significance of IgM antibody response to hepatitis C virus core protein in patients with chronic hepatitis C." Hepatology. 22. 402-406 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naito M.,et al.: "Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver disease." Hepatology. 22. 407-412 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawanishi Y.,et al.: "Tumor necrosis factor-alfa and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells." J Med Virol. 47. 272-277 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takehara T.,et al.: "Expression of hepatitis C virus genome in rat liver after cationic liposome-mediated in vivo gene transfer." Hepatology. 21. 746-751 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hiramatsu N,et al.: "Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C." Hepatology. 19. 1354-1359 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mita E,et al.: "Role of Fas ligand in apoptosis induced by hepatitis C virus infection." Biochem Biophys Res Commun. 204. 468-474 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takehara T,et al.: "Expression of hepatitis C virus genome in rat liver after cationic-liposome mediated in vivo gene transfer." Hepatology. 21. 746-751 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T,et al.: "Density analysis of hepatitis C virus particle population in the circulation of infected hosts : Implications for virus neutralization or persistence." J Hepatol. 22. 440-448 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki N,et al.: "The significance of immunoglobulin M antibody response to hepatitis C virus core protein in patients with chronic hepatitis C." Hepatol. 22. 402-406 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naito M,et al.: "Serum hepatitis C virus RNA quantity and histological features of hepatitis C virus carriers with persistently normal ALT levels." Hepatology. 19. 871-875 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yuki N,et al.: "Hepatitis C virus replication and antibodies to structural and nonstructural viral proteins in chronic hepatitis C." J Hepatol. 20. 421-425 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mita E,et al.: "Hepatitis C virus genotype and RNA titer in the progression of type C chronic liver disease." J Hepatol. 21. 468-473 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kawanishi Y,et al.: "Tumor necrosis factor-alfa and interferon-gamma inhibit synergistically viral replication in hepatitis B virus-replicating cells." J Med Virol. 47. 272-277 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T,et al.: "Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-alfa." J Med Virol. 46. 230-237 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yamamoto M,et al.: "In vivo transfection of hepatitis C virus complementary DNA into rodent liver by asialoglycoprotein receptor mediated gene delivery." Hepatology. 22. 847-855 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Moribe T,et al.: "Hepatitis C viral complexity detected by single-strand conformation polymorphism and response to interferon therapy." Gastroenterology. 108. 789-795 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Ohkawa K,et al.: "Long-term follow-up of hepatitis B virus and hepatitis C virus replicative levels in chronic hepatitis patients coinfected with both viruses." J Med Virol. 46. 258-264 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Horimoto M,et al.: "Expression and phosphorylation of rat c-met/hepatocyte growth factor receptor during rat liver regeneration." J Hepatol. 23. 174-183 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Kanto T,et al.: "Density analysis of hepatitis C virus particle population in the circulation of infected hosts : Implications for virus neutralization or persistence." J Hepatol. 22. 440-448 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kanto T,et al.: "Serial density analysis of hepatitis C virus particle populations in chronic hepatitis C patients treated with interferon-a." J Med Virol. 46. 230-237 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yuki N,et al.: "The significance of IgM antibody response to hepatitis C virus core protein in patients with chronic hepatitis C." Hepatology. 22. 402-406 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naito M,et al.: "Hepatitis C viral quasispecies in hepatitis C virus carriers with normal liver enzymes and patients with type C chronic liver lisease." Hepatology. 22. 407-412 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Kawanishi Y,et al.: "Tumor necrosis factor-a and interferon-gamma inhibit synergistioally viral replication in hepatitis B virus-replicating cells." J Med Virol. 47. 272-277 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Takehara T,et al.: "Expression of the hepatitis C virus genome in rat liver after cationic liposome-mediated in vivo gene transfer." Hepatology. 21. 746-751 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Mita E,Hayashi N,Hagiwara H,et al.: "Predicting interferon therapy efficacy from hepatitis C virus qenotype and RNA titer." Digestive Diseases and Sciences. 39. 977-982 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Hiramatsu N,Hayashi N,Katayama K,et al.: "Immunohistochemical detection of Fas antigen in liver tissue of patients with chronic hepatitis C." Hepatology. 19. 1354-1359 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanazawa Y,Hayashi N,Mita E,et al.: "Influence of viral quasispecies on effectiveness of interferon therapy in chronic hepatitis C patients." Hepatology. 20. 1121-1130 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yuki N,Hayashi N,Hagiwara H,et al.: "Hepatitis C virus antibodies and virus replication in asymptomatic blood donors." Vov Sanguinis. 67. 280-285 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Kanto T,Hayashi N,Takehara T,et al.: "Density analysis of hepatitis C virus particle populatio in the circulation of infected hosts." Journal of Hepatology. (in press).

    • Related Report
      1994 Annual Research Report
  • [Publications] Mita E,Hayashi N,Iio S,et al.: "Role of Fas ligand in apoptosis induced by hepatitis C virus infection." Biochem Biophys Res Commun. 204. 468-474 (1994)

    • Related Report
      1994 Annual Research Report

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Published: 1994-04-01   Modified: 2016-04-21  

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