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FLUCTUATION OF INNATE IMMUNE SYSTEM IN VIRAL INFECTED NEURONAL CELIS

Research Project

Project/Area Number 18590452
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Virology
Research InstitutionSapporo Medical University

Principal Investigator

FUJIE Nobuhiro  Sapporo Medical University, SCHOOL OF MEDICINE, PROFESSOR (90133719)

Co-Investigator(Kenkyū-buntansha) YOKOTA Shin-ichi  SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR (10325863)
OKABAYASHI Tamaki  SAPPORO MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, INSTRUCTOR (10359995)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥4,010,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥510,000)
Fiscal Year 2007: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2006: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsVirus / Innate immunity / Neuronal cells / Interferon / Toll-like receptor / Signal transduction pathway / Toll-like receptor / インターフェロン / 神経細胞 / 情報伝達系 / 麻疹ウイルス / 単純ヘルペスウイルス / ムンプスウイルス
Research Abstract

Fluctuation of innate immunity, interferon (EFN) system and receptor (TLR) signaling pathway, was investigated in viral infected human neuronal cell lines, U118-MG (human glioblastoma), MO3.13 (human oligodendroglial cell), ST88-14 (human malignant schwannoma cell) and NT2 (cloned human embryonal carcinoma cell).
1. IFN signaling pathway:
Induction of IFN-inducible genes, oligo-2', 5'-adenylate synthetase (2-5AS) and MxA, was recognized in all of these cell lines after treatment with ITN- α, ITN- β or IFN- γ. Although these cell lines show normal response activity to WNs, induction of IFN- y signaling pathway was not found in M03.13, ST88-14 and NT2 cell lines.
Interestingly, TLR4 was induced in treatment of NT2 cells with IFN- γ in spite of no induction of 2-5AS.IFN- α / β, IFN- γ signal transduction pathway was blacked by mumps virus (MuV) infected these neuronal cell lines because of the degradation of STAT-1 and STAT-3. Furthermore, as is naturally expected, measles virus (MeV) also inhibited the IFN-α/β signaling pathway. Nevertheless the dysfunction of IFN signaling, MuV and MeV were able to induce NDA5, which invoves in IFN production, in virus infected these cell lines. It is suggested that induction of the MDA5 is dependent on viral protein (s), but not by IFNs or other cytokines.
2. TLR expression and TLR signaling pathway :
TLR3 was not found in these four neuronal cell lines, and IFNs (α, β and γ) treatment was not effectable in induction of TLR3. Expression of TLR4 was found in these cells with the exception of NT2. TLR7 was not in U118-MG. Induction of TLR4 in NT2 and TLR7 in U118-MG recovered by IFN treatment. Fluctuation of ThRs expression by virus infection was not recognized in these cell lines. Production of cytokines (IL-6, IL-8 and RANTES) by virus infection in these cell lines was lower than those in epithelium cell lines.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (20 results)

All 2008 2007 2006 2005

All Journal Article (12 results) (of which Peer Reviewed: 6 results) Presentation (6 results) Book (2 results)

  • [Journal Article] Measles virus P protein suppresses Toll-like receptor signal throughup-regulation of ubiquitin-modifying enzyme A202008

    • Author(s)
      Yokota, S., et. al.
    • Journal Title

      The FASEB Journal 22

      Pages: 74-83

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Measles virus P protein suppresses Toll-like receptor signal through up-regulation of ubiquitin-modifying enzyme A202008

    • Author(s)
      Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N
    • Journal Title

      The FASEB Journal 22

      Pages: 74-83

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Molecular mechanisms for suppression of TLR signaling pathway by virus infection (in Japanease)2008

    • Author(s)
      Fujii, N., Yokota, S., Yokosawa, N., Okabayashi, T
    • Journal Title

      Protein, Nucleic acid and Enzyme 56

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Measles virus P protein suppresses Toll-like receptor signal through Up-regulation of ubiquitin-modifying enzyme A20.2008

    • Author(s)
      Yokota, S., et. al.
    • Journal Title

      The FASEB Journal 22

      Pages: 74-83

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of NF-kB and AP-1 activation in monocytic cellspersistently infected with measles virus2007

    • Author(s)
      Indoh, T., et. al.
    • Journal Title

      Virology 361

      Pages: 294-303

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Highly-purified Helicobacte pylori LPS preparation induce weak inflammatory reactions and utilize Toll-like receptor 2 complex but notToll-like receptor 4 complex2007

    • Author(s)
      Yokota, S., et. al.
    • Journal Title

      FEMS Immunol. Med. Microbiol 51

      Pages: 140-148

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Suppression of NF-kB and AP-1 activation in monocytic Cells persistently infected with measles virus2007

    • Author(s)
      Indoh, T., Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N
    • Journal Title

      Virology 361

      Pages: 294-303

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Highly-purified Helicobacter pylori LPS preparations induce weak inflammatory reactions and utilize Toll-like receptor 2 complex but not Toll-like receptor 4 complex2007

    • Author(s)
      Yokota, S., Ohnishi, T., Muroi, M., Tanamoto, K., Fujii, N. Amano, K
    • Journal Title

      FEMS Immunol. Med. Microbiol 51

      Pages: 140-148

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Suppression of NF-kB and AP-1 activation in monocytic cells persistently infected with measles virus.2007

    • Author(s)
      Indoh, T., et. al.
    • Journal Title

      Virology 361

      Pages: 294-303

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Highly-purified Helicobacter pylori LPS preparations induce weak infla mmatory reactions and utilize Toll-like receptor 2 complex but not Toll-like receptor 4 complex.2007

    • Author(s)
      Yokota, S., et. al.
    • Journal Title

      FEMS Immunol. Med. Microbiol. 51

      Pages: 140-148

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Suppression of NF-kB and AP-1 activation in monocytic cells persistently infected with measles virus.2007

    • Author(s)
      Indoh T, et al.
    • Journal Title

      Virology In press

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Cytokine regulation in SARS coronavirus infection compared to other respiratory virus infection.2006

    • Author(s)
      Okabayashi T, et al.
    • Journal Title

      Journal of Medical virology 78

      Pages: 417-424

    • Related Report
      2006 Annual Research Report
  • [Presentation] 麻疹ウイルスによるインターフェロン/サイトカイン情報伝達系攪乱の多彩なストラテジー。2007

    • Author(s)
      横田伸一
    • Organizer
      日本ウイルス学会総会(シンポジュウム)
    • Place of Presentation
      札幌
    • Year and Date
      2007-10-21
    • Related Report
      2007 Annual Research Report
  • [Presentation] Suppression of Toll-like receptor signaling by measles virus through up-regulation of a host negative regulator A20 by viral P protein2007

    • Author(s)
      Yokota, S., Okabayashi, T., Yokosawa, N., Fujii, N
    • Organizer
      The 20th NAITO Conference
    • Place of Presentation
      Tokyo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Anti-HSP auto-antibodies enhance HSP-induced pro-inflammat- ory cytokine production in human monocytic cells via Toll-like Receptor2007

    • Author(s)
      Yokota, S., Fujii, N
    • Organizer
      The 13th Conference of JAPAN ENDOTOXIN SOCIETY
    • Place of Presentation
      Kagoshima
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Diversity of suppression mechanisms in IFN/TLR signal pathway by measles virus2007

    • Author(s)
      Yokota, S., Fujii, N
    • Organizer
      The 55th Conference of the Japanease Society for Virology (Symposium)
    • Place of Presentation
      Sapporo
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Suppression of innate immunity by measles virus2006

    • Author(s)
      Yokota, S., Okabayashi, T., Indoh, T., Yokosawa, N., Fujii, N
    • Organizer
      The 54th Conference of the Japanease Society for Virology
    • Place of Presentation
      Nagoya.
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 麻疹ウイルスによるインターフェロン1サイトカイン情報伝達系撹乱の多彩なストラテジー2005

    • Author(s)
      横田 伸一、藤井 暢弘
    • Organizer
      第55回日本ウイルス学会学術総会(シンポジュウム)
    • Place of Presentation
      札幌
    • Year and Date
      2005-10-21
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] エンドトキシン研究10(麻疹ウイルス感染によるToll-like receptor情報伝達系の御制とその意義)2007

    • Author(s)
      横田 伸一, 他
    • Total Pages
      11
    • Publisher
      医学図書出版
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Book] エンドトキシン研究10(麻疹ウイルス感染によるToll-like receptor情報伝達系の抑制とその意義)。2007

    • Author(s)
      横田伸一、他
    • Total Pages
      11
    • Publisher
      医学図書出版
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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