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The immunosuppressive function of the α-fetoprotein

Research Project

Project/Area Number 10670131
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathological medical chemistry
Research InstitutionHOKKAIDO UNIVERSITY

Principal Investigator

NISHI Shinzo  Hokkaido Univ., Sch. Med., Pro., 医学部, 教授 (20001894)

Co-Investigator(Kenkyū-buntansha) NAKABYASHI Hidekazu  Hokkaido Univ., Grad. Sch. Med., Inst., 医学部, 助手 (10033383)
SAKAI Masaharu  Hokkaido Univ., Sch. Med., Asso. Pro., 医学部, 助教授 (50162269)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsα-fetoprotein / immunosuperssion / auto-imune doseases / T-cell / hepatocellular cacinoma / transgenic mice / 遺伝子 / 甲状腺炎 / Tリンパ球 / マイトジェン
Research Abstract

α-fetoprotein (AFP) is a serum protein in appreciable amounts in fetal but not in adult serum. However, serum AFP is frequently elevated in patients with hepatocellular carcinomas and yolk sac tumors. Numerous studies have suggested that immunomodulation may be one of the biological functions of AFP. To clarify the biological function of the AFP in vivo, we have established a transgenic mouse, which has a human AFP gene under the control of β-actin promoter. In this mouse, ubiquitous expression of AFP is observed. Using these mice, we have been analyzed experimental autoimmune diseases, such as arthritis, autoimmune thyroiditis and experimental encephalomyelitis. We have showed that development of all these experimental autoimmune diseases were significantly suppressed in AFP produced transgenic mice compared with wild mice. In vitro phytohemagglutinin response of splenocytes from transgenic mice was lower than that from wild mice. Significantly reduced numbers of CD4+, CD8+ thymocytes were found in the transgenic mice. These observations suggest that ubiquitously produced AFP modulate in vivo T cell development and/or T cell dependent immune responses. Now, we have constructed the targeting plasmid for establishment of the AFP gene disrupted mice.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (18 results)

All Other

All Publications (18 results)

  • [Publications] Nishihira J. et al.: "Molecular cloning of hman D-dopachrome tautomerase cDNA : N-Terminal proline is essential for enzyme activation"Biochem.Biophys.Res.Commun.. 243. 538-544 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirokawa J. et al.: "Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes"J.Biochem. 123. 733-739 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsushima-Hibiya Y.et al.: "Rat Maf-Related Factors : The Specificities of DNA Binding and Heterodimer Foemation"Biochem.Biophys.Res.Commun.. 245. 412-418 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura E. et al.: "Modulation of T cell function by alpha-fetoprotein : An in vivo study on porcine thyroid peroxidase-induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein"Tomor Biology. 20. 162-171 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamamoto R. et al.: "A study on the lectin reactivity of alpha-fetoprotein prodeced by hepatoid adenocarcinoma and yolk sac tumors"Tomor Biology. 20. 212-217 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang K. et al.: "Molecular cloning and functional characterization of the mouse mafB gene"Gene. 242. 419-426 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Nishihira, J., Fujunaga, M., Kuriyama, T., Suzuki, M., Sugimoto. H., Nakagawa, A., Tanaka, I., and Sakai, M.: "Molecular cloning of human D-Iopachrome tautomerase CDNA : N-Terminal proline is essential for enzyme activation"Biochem. Biophys. Res. Commun.. 243. 538-544 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Hirokawa, J., Sakaue, S.. Furuya, Y., Ishii, J., Hasegawa, A., Tagami, S., Kawakami, Y., Sakai, M., Nishi, S. and Nishihira, J.: "Tumor necrosis factor-alpha regulates the gene expression of macrophage migration inhibitory factor through tyrosine kinase-dependent pathway in 3T3-L1 adipocytes."J. Biochem.. 123. 733-739 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsushima-Hibiya, Y., Nishi, S., and Sakai, M.: "Rat Maf-Related Factors : The Specificities of DNA Binding and Heterodimer Formation."Biochem. Biophys. Res. Commun.. 245. 412-418 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matsuura, E., Kang, Y., Kitakawa, H., Ogata, A., Kotani, T., Ohtaki, S., Nishi, S.: "Modulation of T cell function by alpha-fetoprotein : An in vivo study on porcine thyroid peroxidase-induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein"Tomor Biology. 20. 162-171 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yamamoto R., Wakui Y., Taketa, K., Ishikura H., Sakuragi, N., hattori R., Sato H., Ebina. Y., Nishi, S., Fujimoto, S.: "A study on the lectin reactivity of alpha-fetoprotein produced by hepatoid adenocarcinoma and yolk sac tumors."Tomor Biology. 20. 212-217 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Huang, K., Serria, M.S., Nakabayas, H., Nishi, S., and Sakai, M.: "Molecular cloning and functional characterization of the mouse mafB gene."Gene. 242. 419-426 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Matusuur, E. et al.: "Modulation of T cell function by alpha-fetoprotein : An in vivo study on porcine thyroid peroxidase-induced experimental autoimmune thyroiditis in transgenic mice producing human alpha-fetoprotein"Tomor Biology. 20. 162-171 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamamoto, R. et al.: "A study on the lectin reactivity of alpha-fetoprotein produced by hepatoid adenocarcinoma and yolk sac tumors"Tombor Biology. 20. 212-217 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Huang, K. et al.: "Molecular cloning and functional characterization of the mouse mafB gene"Gene. 275. 444-450 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Matsushima-Hibiya,Y.,Nishi,S.,Sakai,M.: "The specificities of DNA binding and heterodimer formation." Biochem.Biophys.Res.Commun.245(2). 412-418 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hirokawa,J.,Nishi,S.,et al.: "Tumor necrosis factor α-requlates the gene expression of macrophage migration inhibitory factor" J.Biochemistry. 123. 733-739 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Matsuura,E.,Kang,Y.,Nishi,S.,et al.: "Modulation of T cell function by α-fetoprotein (AFP) : an in vivo study on porcine thyroid peroxidase" Tumor Biology. (in press). (1999)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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