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Analysis of action mechanism of intracellular glutathione redox to control lung inflammation and application to asthma treatment of glutathione modulator

Research Project

Project/Area Number 16590974
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 膠原病・アレルギー・感染症内科学
Research InstitutionGunma University

Principal Investigator

DOBASHI Kunio  GUNMA UNIVERSITY, FACULTY OF MEDICINE, PROFESSOR, 医学部, 教授 (00241894)

Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2005: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2004: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsredox / glutathione / IL-12 / oxidative stress / Th1 / Th2 balance / macrophage / MAP kinase / asthma / TH1 / TH2 / オゾン
Research Abstract

We recently demonstrated that balance of reduced and oxidized glutathione level (GSH/GSSG) in macrophage (MΦ) play a central role in determining which of the TH1 and TH2 cytokine responses predominate during immune states through IL-12 production. And we showed that glutathione redox regulated LPS-induced IL-12 production through p38 MAP kinase activation. On the other hand, c-jun N-terminal kinase negatively regulated LPS-induced IL-12 production from MΦ, and glutathione redox regulates LPS-induced IL-12 production through the opposite control of JNK and p38 MAP kinase activation.
In this project, we revealed that oxidative stress affected intracellular. glutathione redox status in airway epithelial cells and increased production of cytokine. (ref1) And, Our data suggest that the involvement of RhoA/ROCK pathway in TCR-mediated secretion of IFN-gamma and IL-4 in patients with bronchial asthma differed from that in healthy persons. (ref2) Furthermore, we revealed that sphingosine 1-phosphate (S1P_2) attenuated cell migration by inhibiting a Racl-dependent signaling pathway and decreased RANTES production by stimulating a Gαq-dependent mechanism both possibly through the S1P_2 receptors.(ref3) We also revealed that glutathione modulator improved airway hyper responsiveness in OVA induced mouse asthma model and are preparing publication.

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (14 results)

All 2006 2005 2004

All Journal Article (14 results)

  • [Journal Article] Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers2006

    • Author(s)
      Iijima H, Tomizawa Y, Iwasaki Y, Sato K, Sunaga N, Dobashi K, Saito R, Nakajima T, Minna JD, Mori M.
    • Journal Title

      Int J Cancer 118

      Pages: 797-801

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells2005

    • Author(s)
      Kawata T, Ishizuka T, Tomura H, Hisada T, Dobashi K, Tsukagoshi H, Ishiwara M, Kurose H, Mori M, Okajima. F
    • Journal Title

      Biochem Biophys Res Commun. 331

      Pages: 670-7

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005

    • Author(s)
      Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, MInna JD, Nakajima T, Mori M
    • Journal Title

      Clin Cancer Res. 112

      Pages: 6816-22

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Genetic and epigenetic inactivation of LTF gene at 3p21.3 in lung cancers2005

    • Author(s)
      Iijima H, Tomizawa Y, Iwasaki Y, Sato K, Sunaga N, Dobashi K, Saito R, Nakajima T, Minna JD, Mori M
    • Journal Title

      Int J Cancer 118

      Pages: 797-801

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells2005

    • Author(s)
      Kawata T, Ishizuka T, Tomura H, Hisada T, Dobashi K.Tsukagoshi H, Ishiwara M, Kurose H, Mori M, Okajima F
    • Journal Title

      Biochem Biophys Res Commun. 331

      Pages: 670-677

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005

    • Author(s)
      Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, Minna JD, Nakajima T, Mori M
    • Journal Title

      Clin Cancer Res. 112

      Pages: 6816-6822

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Sphingosine 1-phosphate inhibits migration and RANTES production in human bronchial smooth muscle cells2005

    • Author(s)
      Kawata T, Ishizuka T, Tomura H, Hisada T, Dobashi K, Tsukagoshi H, Ishiwara M, Kurose H, Mori M, Okajima, F
    • Journal Title

      Biochem Biophys Res Commun. 331

      Pages: 640-647

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Clinicopathologic Significance of the Mutations of the Epidermal Growth Factor Receptor Gene in Patients with Non-Small Cell Lung Cancer.2005

    • Author(s)
      Tomizawa Y, Iijima H, Sunaga N, Sato K, Takise A, Otani Y, Tanaka S, Suga T, Saito R, Ishizuka T, Dobashi K, Minna JD, Nakajima T, Mori M
    • Journal Title

      Clin Cancer Res. 11

      Pages: 6816-6822

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Helicobacter pylori seroprevalence in patients with mild asthma.2005

    • Author(s)
      Jun ZJ, Lei Y, Shimizu Y, Dobashi K, Mori M.
    • Journal Title

      Tohoku J Exp Med. 207

      Pages: 287-291

    • NAID

      10016785913

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Effect of ozone exposure on intracellular glutathione redox state in cultured human airway epithelial cells.2004

    • Author(s)
      Todokoro M, Mochizuki H, Tokuyama K, Utsugi M, Dobashi K, Mori M, Morikawa A.
    • Journal Title

      Inflammation. 28

      Pages: 105-14

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects2004

    • Author(s)
      Aihara M, Dobashi K, Iizuka K, Nakazawa T, Mori M.
    • Journal Title

      Int Immunopharmacol 4

      Pages: 557-61

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary 2004 Annual Research Report
  • [Journal Article] Effect of ozone exposure on intracellular glutathione redox state in cultured human airway epithelial cells.2004

    • Author(s)
      Todokoro M, Mochizuki H, Tokuyama K, Utsugi M, Dobashi K, Mori M, Morikawa A
    • Journal Title

      Inflammation 28

      Pages: 105-114

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of Y-27632 on release of cytokines from peripheral T cells in asthmatic patients and normal subjects2004

    • Author(s)
      Aihara M, Dobashi K, Iizuka K, Nakazawa T, Mori M
    • Journal Title

      Int Immunopharmacol 4

      Pages: 557-561

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of ozone exposure on intracellular glutathione redox state in cultured human airway epithelial cells.2004

    • Author(s)
      Todokoro M, Mochizuki H, Tokuyama K, Utsugi M, Dobashi K, Mori M, Morikawa A.
    • Journal Title

      Inflammation 28

      Pages: 105-114

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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