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Analysis of the pathomechanism of the demyelinating diseases and the searach for the therapy

Research Project

Project/Area Number 07670373
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionKYUSHU UNIVERISTY

Principal Investigator

HARA Hideo  Kyushu Univ.Medicine lecturer, 医学部, 助手 (00260381)

Co-Investigator(Kenkyū-buntansha) WATANABE Takeshi  Kyushu Univ.Professor, 生体防御医学研究所, 教授 (40028684)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥1,300,000 (Direct Cost: ¥1,300,000)
KeywordsHTLV-I / rolipram / ICAM1 / gag / HTLV-1 / TCR / Vβ / ICAM-I / 細胞内シグナル
Research Abstract

Previous studies reported that production of proinflammatory cytokines, such as TNF-alpha and IFN-gamma, were increased in the serum and the CSF of HAM patients. These cytokines may play an important role in the pathogenesis of HAM/TSP.We examined the effect of PDE-IV inhibitor rolipram on the cytokines production in HTLV-I infected cell lines and PBMCs of HAM patients. PBMCs and HTLV-I infected T cell lines (HUT102, MT2) were cultured with different dose of rolipram in 10% FCS/RPMI1640. Supernatants of cultured cells were harvested after five days. Cytokines were determined by ELISA kits for TNF-alpha, INF-gamma, TGF-beta. RNA were extracted from the cultured PBMSCs and T cell lines. cDNA was synthesized and amplified with primers specific for TNF-alpha, EFN-gamma, TGF-beta by RT-PCR.Rolipram inhibited TNF-alpha production by PBMCs from all HAM patients and HUT102 in dose dependent manner. Production of IFN-gamma was less strongly suppressed in some HAM patients. Concentration of TGF-beta in culture supernatants was not influenced by rolipram. These findings suggest the possibility of rolipram as potential therapy for HAM/TSP.
Intercellular adhesion molecule 1 (ICAM 1) is an inducible protein ligand which is up-regulated during inflammation and is either not consitutively expressed or expressed at low levels. The expression of ICAM1 is increased HTLV-I infected T cell lines as well as in CD4+ T cells of peripheral blood lymphocytes (PBLs) from HAM/TSP patients. After PBLs of HAM patients were cultured in the presence of stimulating anti-ICAM1 antibody, the expression of HTLV-I gag protein in PBLs was observed by the immuno-histostainning and western bloting using HTLV-I antigen specific mouse monoclonal antibody. These data suggested that the signal transduction via adhesion molecule ICAM1 could induce the transcription of HTLV-I gene and this might play an important role in the pathogenesis of HAM/TSP.

Report

(3 results)
  • 1996 Annual Research Report   Final Research Report Summary
  • 1995 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 原英夫: "脱髄性神経免疫疾患-多発性硬化症,HAM/TSP" 細胞工学. 14. 305-311 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 原英夫: "HAM/TSPにおけるT細胞" 免疫Immunology Frontier. 5. 213-215 (1955)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomoko Hatae,Hideo Hara: "The effect of rolipram on the production of cytokines in HTLV-I infected cell lines and peripehral blood mononuclear cells of patients with HTLV-I-associated myelopathy (HAM)" J.Neurol.Sci.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akifumi Yamamoto,Hideo Hara: "Induction of the expression of gag protein in HTLV-I infected lymphocytes by anti-ICAM1 antibody in vitro" J.Neurol.Sci.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hiroyuki Murai,Hideo Hara: "Possibel role of CD23 in the pathogenesis of myashenia gravis : Immunohistochemical and ELISA study." J.Neuroimmunol.(in press). (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 原英夫: "HAM/TSP発症機構の解析" 医学のあゆみ. 177. 939 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] 藤本美加、原英夫: "同心円硬化症(Balo病)" Clinical Neuroscience. 15. 165 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Hatae T,et al.: "The effect of rolipram on the production of cytokines in HTLV-I infected cell lines and peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy (HAM)." J.Neurol.Sci.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yamamoto A,et al: "Induction of the expression of gag protein in HTLV-I infected lymphocytes by anti-ICAM 1 antibody in vitro." J.Neurol.Sci.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Murai H,et al: "Possible role of CD23 in the pathogenesis of myasthenia gravis : Immunohistochemical and ELISA study." J.Neuroimmunol.(in press). (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tomoko Hatae,Hideo Hara: "The effect of rolipram on the production of cytokines in HTLV-I infected cell lines and peripheral blood mononuclear cells of patients with HTLV-I-associated myelopathy(HAM)" J.Neurol.Sci.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Akifumi Yamamoto,Hideo Hara: "Induction of the expression of gag protein in HTLV-I infected lymphocytes by anti-ICAM1 antibody in vitro" J.Neurol.Sci.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroyuki Murai,Hideo Hara: "Possible Role of CD23 in the Pathogenesis of Myasthenia Gravis:Immunohistochemical and ELISA study" J.Neuroimmunol.(in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 原 英夫: "HAM/TSP発症機構の解析" 医学のあゆみ. 177. 939 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 藤本美加、原 英夫: "同心円硬化症(Balo病)" Clinical Neuroscience. 15. 165 (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 原英夫: "脱髄性神経免疫疾患-多発性硬化症,HAM/TSP" 細胞工学. 14. 305-311 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] 原英夫: "HAM/TSPにおけるT細胞" 免疫Immunology Frontier. 5. 213-215 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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