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Glial Response and Neuronal Cell Death Induced by HTLV-I Infected Cells

Research Project

Project/Area Number 07670717
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionNagasaki University

Principal Investigator

SHIRABE Susumu  Nagasaki University School of Medicine, Hospital, Assistant, 医学部・附属病院, 助手 (40264220)

Co-Investigator(Kenkyū-buntansha) NAKAMURA Tatsufumi  Nagasaki University School of Medicine, Hospital, Lecturer, 医学部・附属病院, 講師 (00198219)
Project Period (FY) 1995 – 1996
Project Status Completed (Fiscal Year 1996)
Budget Amount *help
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1995: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsHTLV-I / glia / astrocyte / microglia / macrophage / cerebellar granular cell / nitric oxide / inducible nitric oxide synthase / HTLV-I関連脊髄症 / 初代培養神経細胞 / 神経細胞死
Research Abstract

Although pathogenesis of HTLV-I associated myelopathy has been extensively studied, the mechanism of cell damage constructing central nervous system is still unclear. On the other hand, primary culture procedures of neuron and glial cells are now established and available for a cellular model for viral infections.
In this study, we tried to investigate the mechanisms of in-vitro neuronal and glial cell death as a result of HTLV-I infection.
First of all, we investigated the effect of HTLV-I infected cells such as MT-1, MT-2, HCT-1, W7TM-I and lymphocytes derived from HAM patients against the primary cerebellar granular cells of rats. 1. Supernatants of MT-1 and MT-2 damaged the cerebellar granular cells in dose-dependent manner. The evaluation was performed by MTT assay and fluorescin diacetate assay. Anti-P40tax (tax protein) antibody failed to neutralized this cell damage, suggesting p40tax may affecting expression of cellular factors such as inflammatory cytokines.
Tax gene which is integrated into expression vector was transfected into primary astrocytes, microglia and cerebellar granular cells, respectively. Only few cells can be transfected by lipofectoamine system in each experiment, indicating this method is not available for primary cells.
So, we proceeded to use cell lines to try to determine whether tax-transfected cells can produce cytotoxic factors. Macrophage cell line, U937 supposed to be a model of microglial cells were transfected with tax gene. We disclosed that tax-transfected U937 were over-expressing inducible nitric oxide synthase (iNOS) by semi-quantitative PCR.Direct evidence for over-production of NO was measured by detecting using chemiluminescence and adding Vanadium (III)(FES-450, Scholar-Tee Co., Ltd., Japan). These exaggerated NO production were enhanced by gamma-IFN.This result indicating that microglia/macrophage might damage neuronal cells by exaggerated NO production.

Report

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

    (46 results)

All Other

All Publications (46 results)

  • [Publications] Hiroko Watanabe,et al.: "Exaggerated messenger RNA expression of inflammatory cytokines in human T-lymphotropic virus type I-associated myelopathy." Arch.Neurol.52. 276-280 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tatsufumi Nakamura,et al.: "Pentoxifylline treatment in HTLV-I associated myelopathy." Int.Med.34. 460- (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taro Yamamoto,et al.: "Inhibitory activity in saliva of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro evaluation of saliva as an alternative source of transmission." J.Clin.Microbiol.33. 1510-1515 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshitomo Takahashi,et al.: "Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease." Hum Mol Genet. 5. 81-84 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihito Suenaga,et al.: "Specificity of autoantibodies react with ω-conotoxin MVIIC-sensitive calcium channe in Lambert-Eaton myasthenic myasthenic syndrome." Muscle Nerve. 19. 1166-1168 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suehiro Sakaguchi,et al.: "Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene." Nature. 380. 11- (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tatsufumi Nakamura,et al.: "Spontaneous proliferation of and cytokine production by T cell adherent to human endothelial cells in patients with human T-lymphotropic virus type I-associated Myelopathy" Internal Med.35. 195-199 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshihiro Nishiura,et al.: "Increased production of inflammatory cytokines in cultured CD4_+ cells from patients with HTLV-I- associated myelopathy." Tohoku J Exp Med.179. 227-233 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katsuhiro Ichinose,et al.: "Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I associated myelopathy." Immunobiology. 196. 485-490 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jun Suzuki,et al.: "The association of antibodies against human T cell lymphotropic virus type I ( HTLV-I ) pX gene mutant products with HTLV-I- associated myelopathy/tropical spastic paraparesis." J Infect Dis. 173. 1115-1122 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S Shirabe,et al.: "Altered intermediate filament expression in human neuroblastoma cells transformed by a growth-promoting agent derived from schizophrenic CSE" Cell Mol Neurobiol. 17. 1-12 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira Tsujino,et al.: "Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated myelopathy." 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] Kiyoshi Migita,et al.: "Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy." Transplantation. (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] Hideki Nakamura,et al.: "High prevalence of Sjogren syndrome in patients with HTLV-I-associated myelopathy." Ann Rheumatic Dis.(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] Takafumi Furuya,et al.: "Heightened transmigrating activity of CD4_- positive T cells through reconstituted basement membrane in patients with human T lymphotropic virus type I-associated myelopathy." Proc Assoc Amer Phys. (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] Susumu Shirabe,et al.: "A successful application of pentoxifylline in treatment of HTLV-I associated myelopathy." 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] Hiroko Watanabe, et al: "Exaggerated messenger RNA expression of inflammatory cytokines in human T-lymphotropic virus type I-associated myelopathy" Arch Neurol. 52. 276-280 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tatsufumi Nakamura., et al: "Pentoxifylline treatment in HTLV-I associated myelopathy" Int Med. 34 (5). 460 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Taro Yamamoto, et al: "Inhibitory activity in saliva of cell-to-cell transmission of human T-cell lymphotropic virus type 1 in vitro : evaluation of saliva as an alternative source of transmission" J Clin Microbiol. 33 (6). 1510-1515 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshitomo Takahashi, et al: "Characterization of a nonsense mutation in the ceruloplasmin gene resulting in diabetes and neurodegenerative disease" Hum Mol Genet. 5 (1). 81-84 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akihito Suenaga, et al: "Specificity of autoantibodies react with omega-conotoxin MVIIC-sensitive calcium channel in Lambert-Eaton myasthenic myasthenic syndrome" Muscle Nerve. 19. 1166-1168 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Suehiro Sakaguchi, et al: "Loss of cerebellar Purkinje cells in aged mice homozygous for a disrupted PrP gene" Nature. 380. 11 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Tatsufumi Nakamura, et al: "Spontaneous proliferation of and cytokine production by T cell adherent to human endothelial cells in patients with human T-lymphotropic virus type I-associated Myelopathy" Internal Med. 35 (3). 195-199 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Yoshihiro Nishiura, et al: "Increased production of inflammatory cytokines in cultured CD4+ cells from patients with HTLV-I-associated myelopathy" Tohoku J Exp Med. 179. 227-233 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Katsuhiro Ichinose, et al: "Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I associated myelopathy" Immunobiol. 196. 485-490 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Jun Suzuki, et al: "The association of antibodies against human T cell lymphotropic virus type I (HTLV-I) pX gene mutant products with HTLV-I-associated myelopathy/tropical spastic paraparesis" J Infect Dis. 173. 1115-1122 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] S Shirabe, et al: "Altered intermediate filament expression in human neuroblastoma cells transformed by a growth-promoting agent derived from schizophrenic CSF" Cell Mol Neurobiol. 17. 1-12 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1996 Final Research Report Summary
  • [Publications] Akira Tsujino, et al: "Pentoxifylline down-regulates adhesion molecule expression and inflammatory cytokine production in cultured peripheral blood mononuclear cells from patients with HTLV-I-associated myelopathy" 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] Kiyoshi Migita, et al: "Apoptosis induction in human peripheral blood T lymphocytes by high-dose steroid therapy" Transplantation. 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] Hideki Nakamura, et al: "High prevalence of Sjogren syndrome in patients with HTLV-I-associated myelopathy" Ann Rheumatic Dis. 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] Takafumi Furuya, et al: "Heightened transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T lymphotropic virus type I-associated myelopathy" Proc Associ Amer Phys. 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] Susumu Shirabe, et al: "A successful application of pentoxifylline in treatment of HTLV-I associated myelopathy" 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] T Nakamura,et al.: "Spontaneous proliferation of and cytokine production by T cells adherent to human endothelial cells in patients with human T-lymphotropic virus type I-associated myelopathy." Internal Med. 35. 195-199 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y Nishimura,et al.: "Increased production of inflammatory cytolines in cultured CD4+ cells from patients with HTLV-I-associated myelopathy." Tohoku J Exp Med. 179. 227-233 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K Ichinose,et al.: "Characterization of T cells transmigrating through human endothelial cells in patients with HTLV-I associated myelopathy." Immunobiol. 196. 485-490 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S Shirabe,et al.: "Altered intermediate filament expression in human neuroblastoma cells translormed by a growth-promoting agent derived from schizophrenic CSF." Cells Mol Neurobiol. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] A Tsujino,et al.: "Pentoxifyline down-regulates adhesion molecule expresson and inflammatory cytokine production in cutured peripheral blood mononuclear cells from patients with HTLV-I-associated myelopathy." J Neuroimmunol. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] H Nakamura,et al.: "High prevakence of Sjoren′s syndrome in-patients with HTLV-I-associated myelopathy." Ann Rheumatic Dis. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] S Shirabe,et al.: "A successful application of pentoxifylline in treatment of HTLV-I-associated myelopathy" J.Neurol.Sci. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] T Furuya,et al: "Heightend transmigrating activity of CD4-positive T cells through reconstituted basement membrane in patients with human T lymphotropic virus type I-associated myelopathy." Proceedings of the Assosiation of American Physicians. (in press). (1997)

    • Related Report
      1996 Annual Research Report
  • [Publications] 調 漸: "HAMに対するペントキシフィリンの有用性の検討" Clinical Pharmacotherapy. 2. 257-259 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Hiroko Watanabe,et al: "Exaggerated messenger RNA expression of inflammatory cytokines in human T-lymphotropic virus type I-associated myelopathy." Archives of Neurology. 52. 276-280 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tatsufumi Nakamura,et al: "Pentoxifylline treatment in HTLV-I-associated myelopathy." Internal Med. 34. 460 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Taro Yamamoto,et al: "Inhibitory activity in saliva of cell-to-cell transmission of human T-cell lymphotropic virus type I in vitro : Evaluation of saliva as an alternative source of transmission." J.Clin.Microbiol. 33. 1510-1515 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Tatsufumi Nakamura,et al: "Spontaneous proliferation of and cytokine production by T cells adherent to human endothelial cells in patients with human T-lymphotropic virus type I-associated myelopathy." Internal Med.(1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Jun Suzuki,et al: "The association of antibodies against human T cell lymphotropic virus type I (HTLV-I) px gene mutant in HTLV-I-associated myelopathy/tropical spastic paraparesis." J.Infect Dis. (1996)

    • Related Report
      1995 Annual Research Report

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

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