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The role of microglia in the pathogenesis of the central nervous system

Research Project

Project/Area Number 04670504
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 Univ., Dept.Neurol., Assist.Prof., 医学部, 講師 (50196896)

Co-Investigator(Kenkyū-buntansha) SAWADA Makoto  Fujita Health Univ., Cell.Biol., Assist.Prof., 医学部, 講師 (10187297)
YAMAMOTO Hiroko  Fujita Health Univ., Dept.Neurol., Prof., 医学部, 教授 (20148258)
Project Period (FY) 1992 – 1994
Project Status Completed (Fiscal Year 1994)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1994: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥700,000 (Direct Cost: ¥700,000)
KeywordsMicroglia / Cytokine / IL-10 / Astrocyte / IL-4 / Retrovirus / サイトカインネットワーク / HIV / CD4
Research Abstract

In this study we aimed to approach the origin and function of microglia, roles of microglia in the cytokine network in the central nervous system (CNS) and in the pathophysiology of CNS disorders. Microglia was shown to be regulated for their proliferation and differentiation by colony stimulating factor as was peripheral macrophages. However, the effects of macrophage-deactivating cytokines such as IL-4, IL-10 and TGFbeta on microglia were different from those on macrophages. All three cytokines suppressed cytokine production by CNS cells. But, IL-4 induced proliferation of microglia but not in macrophages. IL-10 down-regulated the expression cytokine receptors in microglia but not in macrophages. Since we have shown that IL-10 is produced by microglia and astrocytes and the receptors are expressed by these cells, these cytokines may play a role in the CNS cytokine network as a negative regulators, functioning differently from peripheral immune system. We also found that the glial cells produced IL-5 whose functions are as yet unknown.
Although a variety of cytokines are produced in the CNS,most of them were induced in the pathological conditions. We only detect IL-1, TNFalpha and M-CSF mRNA in the normal adult brain. We also found the microglia responded to produce cytokine much faster than other glial cells and the cytokine produced by microglia such as TNFalpha or IL-1 induced IL-6 production in astrocytes. Taking altogether, we assume microglia have some different characteristic from macrophages and play a major regulatory role in the cytokine network in the CNS.

Report

(4 results)
  • 1994 Annual Research Report   Final Research Report Summary
  • 1993 Annual Research Report
  • 1992 Annual Research Report
  • Research Products

    (33 results)

All Other

All Publications (33 results)

  • [Publications] Suzumura,A.et.al: "IL-4 induces proliferation and activation of microglia but suppreses their induction of class II MHC autigen expression" J.Neuroimmunol.53. 209-218 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzumura,A.et al.: "TGFB suppresses activation and proliferation of microglia in vitro" J.Immunol.151. 2150-2158 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzumura,A.et.al.: "Effects of microglia-derived ug tokiros on a strocyte proliferation" Restrative Neurol.Neurosci. 5. 347-352 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 錫村明生: "神経系におけるサイトカインネットワーク" 日本臨床. 52. 2887-2893 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 錫村明生: "サイトカインと免疫応答" 臨床免疫. 27. 376-382 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] 錫村明生: "サイトカインと脳機能" 蛋白核酸酵素. (印刷中). (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno, T., Sawada, M., Marunouchi, T., and Suzumura, A.: "Production of interleukin-10 by mouse glial cells in culture." Biochem.Biophys.Res.Comm.205. 1907-1915 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Yu, F., Itoyama, Y., Kira, J., Fijiwara, K., Kobayashi, T., Kitamoto, T., Suzumura, A., Yamamoto, N., Nakajima, Y., and Goto, I.: "TNFb produced by HTLV-1-infected cells influences the proliferation of human endothelial cells and fibroblasts." J.Immunology. 152. 5930-5938 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Mizuno, T., Sawada, M., Suzumura, A.and Marunouchi, T.: "Expression of cytokines during glial differentiation." Brain Res.656. 141-146 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzumura, A., Sawada, M., Ito, Y., and Marunouchi, T.: "IL-4 induces proliferation and activation of microglia but suppresses their induction of class II major histocompatibility complex antigen expression." J.Neuroimmunol.53. 209-218 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sawada, M., Itoh, Y., Suzumura, A., and Marunouchi, T.: "Expression of cytokine receptors in cultured neuronal and glial cells." Neurosci.Lett.160. 131-134 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzumura, A., Sawada, M., Yamamoto, H.and Marunouchi, T.: "Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro." J.Immunol.151. 2150-2158 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Imamura, K., Suzumura, A., Hayashi, F.and Marunouchi, T.: "Cytokine production by peripheral blood monocyte/macrophages in multiple sclerosis patients." Acta Neurol.Scandinav.87. 281-285 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sawada, M., Suzumura, A., Itoh, Y.and Marunouchi, T.: "Production of interleukin-5 by mouse astrocytes and microglia in culture." Neurosci.Lett.155. 175-178 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Sawada, M., Suzumura, A., Ohno, K., and Marunouchi, T.: "Regulation of astrocyte proliferation by prostaglandin E_2 and the a subtype of protein kinese C." Brain Res.613. 67-73 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1994 Final Research Report Summary
  • [Publications] Suzumura,A.et al.: "Interleukin-4 induces proliferation and activation of microgl:abu T suppresses thein induction of class II MHC ontigen expressiou" J.Neuroimmunol,. 53. 209-218 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mizuno,T.et al.: "Expression of cytokines duriyg differeutiation" Braiu Research. 656. 141-146 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Mokuno,K.et al.: "Induction of Mu SOD by cytokiues and LPS in astrocytes" J.Neurochem.63. 612-616 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 錫村明生: "神経系におけるサイトカインネットワーク" 日本臨床. 52. 2887-2893 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] 錫村明生: "サイトカインと免疫応答" 臨床免疫. 27. 376-382 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] 錫村明生: "サイトカインと脳機能" 蛋白核酸酵素. (印刷中). (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Suzumura,A.,Sawada,M.,Yamamoto,H.et al.: "Transforming growth factor-beta suppresses activation and proliferation of microglia in vitro." J.Immunology. 151. 2150-2158 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Suzumura,A.,Sawada,M.,Mokuno,K.et al.: "Effects of microglia-derived cytokines on astrocyte proliferation." Restrative Neurol.Neurosci.5. 347-352 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sawada,M.,Ito,Y.,Suzumura,A.et al.: "Expression of cytokine receptors in cultured neuronal and glial cells." Neurosci.Lett.160. 131-134 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sawada,M.,Suzumura,A.,et al.: "Production of interleukin-5 by mouse astrocytes and microglia in culture." Neurosci.Lett.155. 175-178 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sawada,M.,Suzumura,A.,et al.: "Regulation of astrocyte proliferation by prostaglandin E2 and the alpha type of protein kinase C." Brain Research.613. 67-73 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 錫村明生: "神経系のサイトカインネットワーク" 実験医学. 11. 133-138 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] 錫村 明生: "サイトカインと脳の成長" 実験医学. 10. 1471-1476 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Suzumura,A.et al.: "Effects of microglia-derived cytokines on astrocyte proliferation." Restorative Neurol.and Neurosci.(1993)

    • Related Report
      1992 Annual Research Report
  • [Publications] SaWada,M.,Suzumura,A.et al.: "TNF alpha induces IL-6 production by astrocytes but not by microglia." Brain Research. 583. 296-299 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sawada,M.,Suzumura,A.et al.: "Induction of cytokines in glial cells by trans activator of human T-cell lymphotropic virus type 1." FEBS Letter. 313. 47-50 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Sawada,M.,Suzumura,A.et al.: "Down regulation of CD4 expression in cultured microglia by immunosuppressants and LPS." Biochem.Biophys.Res.Comm.189. 869-876 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Ohtani,K.,Suzumura,A.et al.: "Establishment of mouse oligodendrocyte/type 2 astrocyte lineage cell line by transfection with origine-defective SV40 DNA." Cell Structure and Function. 17. 325-333 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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