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Functinal analysis of leukotrine C4 synthase gene in the pathogenesis of asthma

Research Project

Project/Area Number 12470137
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionDokkyo University School of Medicine

Principal Investigator

FUKUDA Takeshi  Dokkyo University, School of Medicine, Professor, 医学部, 教授 (90088873)

Co-Investigator(Kenkyū-buntansha) ARIMA Masafumi  Chiba University, Graduate School of Medicine, Assistant Professor, 大学院・医学研究院, 助手 (00202763)
TOKUHISA Takeshi  Chiba University, Graduate School of Medicine, Professor, 大学院・医学研究院, 教授 (20134364)
TAKADA Akira  Dokkyo University, School of Medicine, Assistant Proressor, 医学部, 講師 (90155002)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2000: ¥9,900,000 (Direct Cost: ¥9,900,000)
Keywordsbronchial asthma / leukotriene / prostaglandin / LTC4 synthase / chemokine / BCL6 / ロイコトリエンC4合成酵素 / トランスジェニックマウス / 好酸球 / リンパ球 / eosinophil / FLAP / IL-5 / LTC4
Research Abstract

Mast cells play important roles in allergic airway inflammation by releasing several type cytokines and chemical mediators. Recently it has been reported that these mediators participate broadly in the pathological changes of asthmatuc airways, in addition to bronchial contraction or a blood vessel permeability. Because LTC4 is known to be involved in airway remodeling, and in reinforcement of Th2 type inflammation with PGD2, novel actions of these two mediators have been paid attentions for the pathogenesis of asthma. In this research, we analyzed the roles of LTC4 and PGD2 on asthmatic airway inflammation. For this purpose we made a LTC4 synthase transgenic mice. We have clarified about the following points.
1.LTC4 erinforced production of Th2 cytokine by activated T cells. And up-regulation of cysteinyl leukotriene 1 receptor by IL-13 enables human lung fibroblasts to respond to leukotriene C4 and produce eotaxin.
2.Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine.
3.A transcriptional repressor, BCL6 regulate expression of IL-5 gene and LTC4 synthase gene.
It becomes clear that the LTC4 and PGD2 are aggravation factor of Th2 type inflammation. Moreover, BCL6 is adjusted to restrain to asthmatic inflammation on the gene level of which are IL-5 and LTC4 synthase. It is expectable to lead not only development of the treatment for bronchial asthma, but also to elucidate of the pathogenesis of asthma by these experimental results.

Report

(4 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • Research Products

    (11 results)

All Other

All Publications (11 results)

  • [Publications] Chibana, K., et al.: "Up-regulation of cysteinyl leukotriene 1 receptor by IL-13 enables human lung fibroblasts to respond to leukotriene C4 and produce eotaxin"J.Immunol.. 170. 4290-4295 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda, K., et al.: "Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine."J.Exp.Med.. 198. 533-543 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arima, M., et al.: "A putative silencer element in the IL-5 gene recognized by Bc16."J.Immunol.. 169. 829-836 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asakura T, et al.: "LTC4 in combination with transforming growth factor-b augments extracellular matrix production from human lung fibroblasts"Dokkyo J.Med.Sci.. In press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Chibana, K., et al.: "Up-regulation of cysteinyl leukotriene 1 receptor by IL-13 enables human lung fibroblasts to respond to leukotriene C4 and produce eotaxin"J.Immunol. 170. 4290-4295 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Honda, K., et al.: "Prostaglandin D2 reinforces Th2 type inflammatory responses of airways to low-dose antigen through bronchial expression of macrophage-derived chemokine"J.ExMed.. 198. 533-543 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Arima, M., et al.: "A putative silencer element in the IL-5 gene recognized by Bc16"J.Immunol.. 169. 829-836 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Asakura T, et al.: "Leukotriene C4 in combination with transforming growth factor-b augments extracellular matrix production from human lung fibroblasts"Dokkyo J.Med.Sci.. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hirata, H., et al.: "Production of TARC and MDC by Naive T cells in Asthmatic Patients"J.Clin.Immunol.. 23. 34-44 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Arima, M., et al.: "A putative silencer elememt in IL-5 gene recognized by Bcl6"J.Immunol.. 169. 829-836 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Cheng G., et al.: "Anti-interleukin-9 antibody treatment inhibits airway inflammation and hyperreactivity in mouse asthma model"Am.J.Respir.Crit.Care.Med.. 166. 409-416 (2002)

    • Related Report
      2002 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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