• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

The mechanisms of demyelinating neurological diseases

Research Project

Project/Area Number 01570460
Research Category

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

Allocation TypeSingle-year Grants
Research Field Neurology
Research InstitutionFujita Health University

Principal Investigator

SUZUMURA Akio  Fujita Health University, Department of Neurology, Assistant Prof., 医学部・神経内科, 講師 (50196896)

Co-Investigator(Kenkyū-buntansha) SAWADA Makoto  Fujita Health University Div. Cell Biology, Assistant Prof., 総合医科学研究所・応用細胞学, 助手 (10187297)
YAMAMOTO Hiroko  the same above, Professor, 医学部・神経内科, 教授 (20148258)
Project Period (FY) 1989 – 1991
Project Status Completed (Fiscal Year 1991)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1989: ¥900,000 (Direct Cost: ¥900,000)
KeywordsGlia / Oligodendrocyte / Astrocyte / Microglia / Demylination / Cytokines / MHC antigens / Retrovirus / マクロファ-ジ / 主要組織適合性抗原 / ウイルス / オリゴデンドロサイド / 抗原呈示
Research Abstract

In order to approach the mechanisms of inflammatory demyelination in the central nervous system, we first examined the interaction between oligodendrocytes and immune system. Neither lymphokines, monokisses nor myelin basic protein (MBP) -reactive T cells were cytotoxic to isolated mouse oligodendrocytes in vitro. Microglia and astrocytes failed to present MBP antigen to the MBP-reactive T cell lines, though both cell types were induced to express Ia antigens by gamma-interferon. Crude lymphokines were found to facilitate maturation of oligodendrocytes rather than toxic to these cells.
Second, we analysed the production and pathophysiological functions of cytokines in the CNS. Microglia produced interleukin (IL) -1, 6, TNF-alpha and another unknown factor which induced astrocyte proliferation. This factor may have a role in the development of gliosis. In addition to these cytokines, astrocytes produced M-CSF, GM-CSF, TGF-beta and other unknown factors, one of which facilitated tight junction formation by endothelial cells, and the other factor suppressed the functions of microglia. TGF-beta also suppress the cytokine production by microglia.
Retrovirus infection and transfection of Human T-cell Leukemia Virus Type 1 transactivator also induced IL-1 and IL-6 production, but not TNF-alpha production, by astrocytes. This transfection also induced surface expression of class I major histocompatibility complex antigens on these glial cells. Since overexpression of MHC antigens reportedly induces oligodendrocyte damage, this transfection model may be useful tool to induce de- or dysmyelination.
These observations suggested that immunoregulatory cytokines were produced in the CNS, and these cytokines might play a important role on the cell-cell interaction in neural cells. Virus could be a possible inducer of these cytokines, which then play a significant role on the development of various neurological disorders including inflammatory demyelination.

Report

(4 results)
  • 1991 Annual Research Report   Final Research Report Summary
  • 1990 Annual Research Report
  • 1989 Annual Research Report
  • Research Products

    (40 results)

All Other

All Publications (40 results)

  • [Publications] Suzumura,A.,et al: "Lymphokines facilitate maturation of oligodendrocytes in vitro." Brain Research. 480. 51-57 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura,A.,et al: "Effects of colony stimulating factor on isolated microglia in vitro." J.Neuroimmunology. 30. 111-120 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 錫村 明生: "ウイルスによる脱髄機序ーcoronaウイルス" 最新医学. 44. 1580-1583 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] 錫村 明生: "神経免疫におけるMHCの役割・神経組織のMHC" 最新医学. 44. 1639-1643 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura,A.,et al: "Morphological transformation of microglia in vitro." Brain Research. 545. 301-306 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada,M.,et al: "Production of tumor necrosis factor-alpha by microglia and astrocytes in culture." Brain Research. 491. 394-397 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Imamura,K.,et al: "Generation and characterization of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells." Lab.Investigation. 63. 853-861 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ohno,K.,et al: "Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes." Biochem.Biphys.Res.Comm.169. 719-724 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada,M.,et al: "Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C" Brain Research. 509. 119-124 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada,M.,et al: "Human T-cell leukemia virus type-1 transactivator induces class I major histocompatibility complex antigen expression in glial cells." J.Virology. 64. 4002-4006 (1990)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura,A.,et al: "Effects of microglia-derived cytokines on astrocytic gliosis."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada,M.et al: "TNF induces IL-6 production by astrocytes but not by mictoglia."

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura, A. et al: "Lymphokines facilitate maturation of oligodendrocytes in vitro." Brain Research. 480. 51-57 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura, A. et al: "Effects of colony stimulating factors on isolated microglia in vitro." J. Neuroimmunol.30. 111-120 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura, A. et al: "Morphological transformation of microglia in vitro." Brain Research. 545. 301-306 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada, M. et al: "Production of tumor necrosis factor-alpha by microglia and astrocytes in culture." Brain Research. 491. 394-397 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Lavi, E. et al: "Induction of MHC class I antigens on glial cells is dependent of persistantmouse hepatitis virus infectio." J. Neuroimmunol.22. 107-111 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Imamura, k., et al: "Generation and characterizaion of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells." Lab. Invest.63. 853-861 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Ohno, K., et al: "Production of granulocyte/macrophage colony-stimulating factor by cultured astrocytes." Biochem. Biophys. Res. Comm.169. 719-724 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada, M., et al: "Activation and proliferation of the isolated microglia by colony stimulating factor 1 and possible involvement of protein kinase C." Brain Research. 509. 119-124 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada, M., et al: "Human T-cell leukemia virus type 1 transactivator induces class I major histocompatibility complex antigen expression in glial cells." J. Virology. 64. 4002-4006 (1990)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura, A., et al: "Effects of microglia-derived cytokines on astrocytic gliosis."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada, M., et al: "TNF-alpha induces IL-6 production by astrocytes but not by microglia."

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Sawada, M., et al: "Astrocyte proliferation controlled by gamma-subspecies of protein kinase C and prostaglandin E_2"

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1991 Final Research Report Summary
  • [Publications] Suzumura,A.et.al.: "Morphological transformation of microglia in vitro." Brain Research. 545. 301-306 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Suzumura,A.et al: "Effects of microplia-derived cytokines on astrocytic gliosis."

    • Related Report
      1991 Annual Research Report
  • [Publications] Sawada,M.et al: "TNFα induces IL-6 production by astrocytes but not by microglia."

    • Related Report
      1991 Annual Research Report
  • [Publications] Sawada,M.et al: "Astrocyte proliferation controlled by γ-subspecies of protein kinase C and prostaglandin E_2"

    • Related Report
      1991 Annual Research Report
  • [Publications] 今村 一博ら: "培養ミクログリアの免疫組織学的検討ー機能変化にもとずく染色性の変化についてー" 臨床神経学. 31. 127-134 (1991)

    • Related Report
      1991 Annual Research Report
  • [Publications] Sawada,M.et al.: "Activation and proliferation of the isolated microglia by colony stimulating factorー1 and possible involvement of protein kinase C." Brain Research. 509. 119-124 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] 錫村 明生: "脳の免疫応答細胞:ミクログリア" Dementia. 4. 120-124 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Ohno,K.,Suzumura,A.,Sawada,M.,et al.: "Production of granulocyte/macrophage colony stimulating factor by cultured astrocytes." Biochem.Biophys.Res.Comm.169. 719-724 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Sawada,M,Suzumura,A,et al.: "Human T cell leukemia virus type 1 transactivator induces class I major histocompatibility complex antigen expression in glial cells." J.Virology. 64. 4002-4006 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Imamura,K.,Ito,M.,Suzumura,A.et al.: "Generation and characterization of monoclonal antibodies against rat microglia and ontogenic distribution of positive cells." Lavoratory Investigation. 63. 853-861 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suzumura,A.,Sawada,M.,Yamamoto,H.,et al.: "Effects of colony stimulating factors on isolated microglia in vitro." J.Neuroimmunology. 30. 111-120 (1990)

    • Related Report
      1990 Annual Research Report
  • [Publications] Suzumura,A.et al.: "Lymphokines facilitate maturation of oligodendrocytes in vitro." Brain Resesrch. 480. 51-57 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sawada,M.et al.: "Production of tumor necrosis factor-alpha by microglia and astrocytes in culture." Brain Reseach. 491. 394-397 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sawada,M.et al.: "Activation and proliferation of the isolated microglia by colony stimulating factor-1 and possible involvement of protein kinase C." Brain Research. 509. 119-124 (1990)

    • Related Report
      1989 Annual Research Report
  • [Publications] Sawada,M.et al.: "HTLV-1 trans-activator induces class I MHC antigen expression in glial cells." J.Virology.

    • Related Report
      1989 Annual Research Report
  • [Publications] Suzumura,A.et al.: "Effects of colony stimulating factors on isolated microgliain vitro." J.Neuroimmunology.

    • Related Report
      1989 Annual Research Report

URL: 

Published: 1989-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi