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Studies on genomic polymorphisms determining host immune reactions against viral infection and interferon therapy

Research Project

Project/Area Number 13670558
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionKeio University

Principal Investigator

SAITO Hidetsugu  Keio University, School of Medicine, Assistant Professor, 医学部, 講師 (80186949)

Co-Investigator(Kenkyū-buntansha) 高木 珠子  慶應義塾大学, 医学部, 助手 (90286469)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2001: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordschronic hepatitis C / hepatitis C virus infection / interferon therapy / IRF-1 gene polymorphisms / promoter activity / T helper function / response to the therapy / インターフェロン治療 / C型肝炎ウイルス感染 / Tヘルパー細胞機能 / 治療反応性 / 生化学的治療反応 / C型ウイルス感染 / Th1 / Th2細胞 / IRF-1 / 遺伝子多型 / 免疫反応
Research Abstract

Interferon regulatory factor (IRF)-1 has been indispensable for the functional activation of T helper 1 (Th1) cytokine release. We investigated promoter polymorphisms (single nucleotide polymorphisms ; SNPs) in the IRF-1 gene to see correlation between SNP types and response to the interferon (IFN) therapy or host immune reaction. Host immune reaction significantly differed according to the SNP types possessed by the host. Th1 reaction was strongly activated with administration of IFN in the host possessing one SNP type, but Th2 reaction was predominant in the host possessing the other type of SNP. These results suggested that the prediction of the host immune reaction in the HCV infection might be possible by checking IRF-1 promoter SNP types, especially in the patients with chronic hepatitis C treated with IFN. Because Th1 function is beneficial for viral elimination and Th2 function may regulate inflammation in the liver. However, the people with Th1-dominant type were few and this SNP types could not explain the response to IFN therapy in the patients. Further investigation including promoter SNPs in the other various cytokines is necessary for clarifying the exact prediction of the IFN therapy in patients with chronic hepatitis C.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (48 results)

All Other

All Publications (48 results)

  • [Publications] Saito H, Tada S, Wakabayashi K, et al.: "The detection of IRF-1 promoter polymorphisms and their possible contribution to T helper response in chronic hepatitis C"J. Interferon Cytokine Res.. 22. 693-700 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyaguchi S, Watanabe T, Takahashi H, et al.: "Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels"Hepatogastroenterology. 49. 724-729 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, H.Ebinuma, H.Nagata, et al.: "Interferon-associated retinopathy in a uniform regimen of natural interferon-a therapy for chronic hepatitis C"Liver. 21. 192-197 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Atsukawa, H.Saito, N.Tsukada, et al.: "Th1 and TH2 cytokines dirrentially regulate the treansformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation"Hepatol. Res.. 20. 193-206 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, S.Tada, H.Ebinuma, et al.: "Interferon regulatory factor-1 promoter polymorphism and response to type 1 interferon"J. Cell. Biochem.. 81. 191-200 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 齋藤英胤, 若林寛二, 高木珠子他: "慢性肝炎に対するインターフェロン治療におけるTh1/Th2バランスと転写因子IRF-1の遺伝子多型との関係"消火器と免疫. 37. 9-11 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Saito, Y.Kanai, M.Sakamoto, et al.: "Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis"Hepatology. 33. 561-568 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Nakamura, H.Saito, H.Ebinuma, et al.: "Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor"J. Cell. Physiol.. 187. 392-401 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Ebinuma, H.Saito, K.Wakabayashi, et al.: "Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells"J. Cell. Physiol.. 188. 56-66 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Saito, H.Saito, M.Nakamura, et al.: "Effect of the molar ratio of branched-chain to aromatic amino acids on growth and albumin mRNA expression of human liver cancer cell lines in a serum-free medium"Nutr. Cancer. 39. 126-131 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, H.Ebinuma, H.Nagata, et al.: "Interferon-associated retinopathy in a uniform regimen of natural interferon-a therapy for chronic hepatitis C"Liver. 21. 192-197 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Ohiishi, H.Saito, N.Tsusaka, et al.: "Anti-fibrogenic effect of an angiotensin II converting enzyme inhibitor on chronic carbon tetrachroride-induced hepatic fibrosis in rats"Hepatol. Res.. 21. 147-158 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Hirokawa, S.Miura, H.Kishikawa, et al.: "Loading of mechanical pressure activates mitogen-activated protein kinase and ealy immediate gene in intestinal epithelial cells"Dig. Dis. Sci.. 46. 1993-2003 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Yoshida, S.Miura, H.Kishikawa, et al.: "Fatty acids enhance GRO/CINC-1 and interleukin-6 production in rat intestinal epithelial cells"J. Nutr.. 131. 1943-1950 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai N, Tsuchimoto K, Tsunematsu S, et al.: "H. Inhibition of growth of human hepatoma cells by dual-function antisense IL-6 oligonucleotides"Hepatol. Res.. 22. 119-126 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishikawa H, Miura S, Yoshida H, et al.: "Transmural pressure induces IL-6 secretion by intestinal epithelial cells"Clin. Exp. Immunol.. 29. 86-91 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zeki S, Miura S, Suzuki H, Watanabe N, Adachi M, Yokoyama H, Horie Y, Saito H, Kato S, Ishii H: "Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats"J. Gastroenterol. Hepatol.. 17. 606-616 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito Y, Kanai Y, Sakamoto M, et al.: "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis"Proc. Natl. Acad. Sci. U.S.A.. 99. 10060-10065 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito H.: "Extrahepatic manifestation in hepatitis C"Jpn. Med. Assoc. J. (JMAJ). 45. 526-531 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M, Saito H, Atsukawa K, et al.: "Bcl-2 prevents doxorubicin-induced apoptosis of human liver cancer cells"Hepatol. Res.. 25. 192-201 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamoto N, Saito H, Ebinuma H, et al.: "Genomic mutations with amino acid substitutions of circulating hepatitis B virus found in non-B, non-C patients with hepatocellular carcinoma"Intern. Med.. 42. 322-330

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, S.Tada, K.Wakabayashi, et al.: "Trends in Gastroenterology and Hepatology. Millenium 2000"H.Asakura, Y.Aoyagi, S.Nakazawa. 142-146 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Saito, Y.Kanai, M.Sakamoto, H.Saito, H.Ishii, S.Hirohashi: "Expression of mRNA for DNA methyltransferases and methyl-CpG-binding proteins and DNA methylation status on CpG islands and pericentromeric satellite regions during human hepatocarcinogenesis"Hepatology. 33(3). 561-568 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Nakamura, H.Saito, H.Ebinuma, K.Wakabayashi, Y.Saito, T.Takagi, N.Nakamoto, H.Ishii: "Reduction of telomerase activity in human liver cancer cells by a histone deacetylase inhibitor"J.Cell.Physiol.. 187(3). 392-401 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, S.Tada, H.Ebinuma, K.Wakabayashi, T.Takagi, Y.Saito, N.Nakamoto, S.Kurita, H.Ishii: "Interferon regulatory factor-1 promoter polymorphism and response to type 1 interferon"J.Cell.Biochem.. 81(S36). 191-200 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Atsukawa, H.Saito, N.Tsukada, Y.Akiba, K.Toda, N.Kumagai, T.Ohishi, Y.Kamegaya, H.Ishii: "Th1 and TH2 cytokines dirrentially regulate the treansformation of Kupffer cells into multinucleated giant cells but similarly enhance the Kupffer cell-induced hepatic stellate cell proliferation"Hepatol.Res.. 20(2). 193-206 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Ebinuma, H.Saito, K.Wakabayashi, Y.Saito, T.Takagi, N.Nakamoto, S.Kurita, T.Okuyama, H.Ishii: "Reduction of c-myc expression by an antisense approach under Cre/loxP switching induces apoptosis in human liver cancer cells"J.Cell.Physiol.. 188. 56-66 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Saito, H.Saito, M.Nakamura, K.Wakabayashi, T.Tamako, H.Ebinuma, H.Ishii: "Effect of the molar ratio of branched-cnain to aromatic amino acids on growth and albumin mRNA expression of human liver cancer cell lines in a serum-free medium"Nutr.Cancer. 39(1). 126-131 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, H.Ebinuma, H.Nagata, Y.Inagaki, N.Nakamoto, Y.Saito, K.Wakabayashi, T.Takagi, M.Nakamura, H.Katsura, Y.Oguchi, H.Ishii: "Interferon-associated retinopathy in a uniform regimen of natural interferon-α therapy for chronic hepatitis C"Liver. 21. 192-197 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Ohiishi, H.Saito, N.Tsusaka, K.Toda, H.Inagaki, Y.Hamada, N.Kumagai, K.Atsukawa, H.Ishii: "Anti-fibrogenic effect of an angiotensin II converting enzyme inhibitor on chronic carbon tetrachroride-induced hepatic fibrosis in rats"Hepatol.Res.. 21(2). 147-158 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Hirokawa, S.Miura, H.Kishikawa, H.Yoshida, H.Nakamizo, H.Higuchi, R.C.Nakatsumi, H.Suzuki, H.Saito, H.Ishii: "Loading of mechanical pressure activates mitogen-activated protein kinase and ealy immediate gene in intestinal epithelial cells"Dig.Dis.Sci.. 46(9). 1993-2003 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Yoshida, S.Miura, H.Kishikawa, M.Hirokawa, H.Nakamizo, R.C.Nakatsumi, H.Suzuki, H.Saito, H.Ishii: "Fatty acids enhance GRO/CINC-1 and interleukin-6 production in rat intestinal epithelial cells"J.Nutr.. 131(11). 2943-2950 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kumagai N, Tsuchimoto K, Tsunematsu S, Toda K, Takeuchi O, Saito H, Morizane T, Tsuchiya M, Ishii H: "Inhibition of growth of human hepatoma cells by dual-function antisense IL-6 oligonucleotides"Hepatol.Res.. 22(2). 119-126 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kishikawa H, Miura S, Yoshida H, Hirokawa M, Nakamizo H, Higuchi H, Adachi M, Nakatsumi RC, Suzuki H, Saito H, Ishii H: "Transmural pressure induces IL-6 secretion by intestinal epithelial cells"Clin.Exp.Immunol.. 29(1). 86-91 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Zeki S, Miura S, Suzuki H, Watanabe N, Adachi M, Yokoyama H, Horie Y, Saito H, Kato S, Ishii H: "Xanthine oxidase-derived oxygen radicals play significant roles in the development of chronic pancreatitis in WBN/Kob rats"J.Gastroenterol.Hepatol.. 17(5). 606-616 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito Y, Kanai Y, Sakamoto M, Saito H, Ishii H, Hirohashi S: "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis"Proc.Natl.Acad.Sci.U.S.A.. 99(15). 10060-10065 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito H, Tada S, Wakabayashi K, Nakamoto N, Takahashi M, Nakamura M, Ebinuma H, Ishii H: "The detection of IRF-1 promoter polymorphisms and their possible contribution to T helper response in chronic hepatitis C"J.Interferon Cytokine Res.. 22. 693-700 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Miyaguchi S, Watanabe T, Takahashi H, Nakamura M, Saito H, Ishii H: "Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels"Hepatogastroenterology. 49(45). 724-729 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saito H: "Extrahepatic manifestation in hepatitis C"Jpn.Med.Assoc.J. (JMAJ). 45(12). 526-531 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Takahashi M, Saito H, Atsukawa K, Ebinuma H, Okuyama T, Ishii H: "Bcl-2 prevents doxorubicin-induced apoptosis of human liver cancer cells"Hepatol.Res.. 25(2). 192-201 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nakamoto N, Saito H, Ebinuma H, Tada S, Saito Y, Kurita S, Kitamura K, Ishii H: "Genomic mutations with amino acid substitutions of circulating hepatitis B virus found in non-B, non-C patients with hepatocellular carcinoma"Intern.Med.. 42(4). 322-330

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, S.Tada, K.Wakabayashi, T.Takagi, N.Nakamoto, S.Kurita, H.Ishii, eds.by H.Asakura, Y Aoyagi, S. Nakazawa: "Growth inhibition of hepatoma cells by type 1 interferons : modification by mutations in the interferon regulatory factor-1 gene, Trends in Gastroenterology and Hepatology. Millenium 2000"Springer. 142-146 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] H.Saito, S.Tada, K.Wakabayashi et al.: "The detection of IRF-1 promoter polymorphisms and their possible contribution to T helper response in chronic hepatitis C"Jouranal of Interferon and Cytokine Research. 22. 693-700 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Saito: "Extrahepatic manifestation in hepatitis C"Japanese Medical Association Journal. 45・12. 526-531 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Miyaguchi, T.Watanabe, H.Saito, et al.: "Interferon therapy for hepatocellular carcinoma patients with low HCV-RNA levels"Hepatogastroenterology. 49・45. 724-729 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Y.Saito, Y.Kanai, H.Saito et al.: "Overexpression of a splice variant of DNA methyltransferase 3b, DNMT3b4, associated with DNA hypomethylation on pericentromeric satellite regions during human hepatocarcinogenesis"Proceeding of National Academy of Science U.S.A.. 99・15. 10060-10065 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saito H, et al.: "Interferon regulatory factor 1 promoter polymorphism and response to type 1 interferon"J. Cell. Biochem.. 81・S36. 191-200 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] H. Saito: "Trends in Gastroenterology and Hepatology"Asakura H, et a.. 370 (2000)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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