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Novel function of prostaglandin D2 and its metabolites in pathogenesis of immune and allergic diseases as examined by prostaglandin D synthase gene-manipulated mice

Research Project

Project/Area Number 11680642
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Functional biochemistry
Research InstitutionOsaka Bioscience Institute

Principal Investigator

URADE Yoshihiro (2000)  Osaka Biosci.Inst., 2^<nd>.dept., Head, 第2研究部, 研究部長 (10201360)

PINZAR Elena I. (1999)  財団法人 大阪バイオサイエンス研究所, 第2研究部, 研究員 (80311306)

Co-Investigator(Kenkyū-buntansha) MOCHIZUKI Takatoshi  Osaka Biosci.Inst., 2<@D1nd@>D1.dept., Research Associate, 第2研究部, 研究員 (40263933)
HAYAISHI Osamu  Osaka Biosci.Inst., 2<@D1nd@>D1.dept., Research Associate, 第2研究部, 研究員 (40025507)
裏出 良博  財団法人 大阪バイオサイエンス研究所, 第2研究部, 研究部長 (10201360)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordsprostaglandin D2 / transgenic mouse / eosinophil / Th2 cytokine / mast cell / knockout mouse / receptor
Research Abstract

To examine the effects of overproduction of prostaglandin (PG) D2 on the inflammatory and allergic reactions, we generated transgenic (TG) mice that over-expressed human PGD synthase under the control of the a-actin promotor. In an ovalbumin (OVA)-induced asthma model, eosinophils and lymphocytes infiltrated into the bronchoalveolar lavage (BAL) fluid of TG mice more significantly than that of the wild-type (WT) mice, at 1 and 3 days after OVA-challenge. The levels of IL-4, IL-5 and eotaxin in the BAL fluid were also significantly higher in TG mice than those in WT mice, although the IFNa level was decreased in TG mice as compared with WT mice. The increases in Th2 cytokines in the BAL fluid and the extent of lymphocyte accumulation in the lung after OVA-challenge were greatly reduced in PGD2 receptor gene-knockout (DP-/-) mice compared with those in WT mice. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. These results, taken together, indicate that PGD2 acts as a mediator to trigger asthmatic responses. PGD2 is also produced as a major prostanoid in the central nervous system and acts as a potent sleep-inducing substance. We therefore studied the sleep behavior of TG mice. Although no difference was observed in the sleep/awake patterns between WT and TG mice, a striking time-dependent increase in non-rapid eye movement (NREM) sleep was observed in TG mice after stimulation by tail clipping. Induction of NREM sleep in TG mice was positively correlated with the PGD2 production in the brain. Sleep and PGD2 content in the brain were essentially unchanged in WT mice after tail clipping. These results with TG mice demonstrate the involvement of PGD2, PGD synthase, and its gene in the regulation of NREM sleep.

Report

(3 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Kanaoka,Y., et.al.: "Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase."Eur.J.Biochem.. 267. 3315-3322 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pinzar,E.I., et.al.: "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis."J.Biol.Chem.. 27. 31239-31244 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimori,K., et.al.: "Transcriptinal activation of the human hematopoietic prostagalndin D synthase gene in megakaryoblastic cells."J.Biol.Chem.. 275・51. 40511-40516 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Urade,Y.and Hayaishi,O.: "Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase."Biochim.Biophys.Acta. 1482. 259-271 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Urade,Y.and Hayaishi,O.: "Prostaglandin D synthase : Structure and function."Vitamins and Hormones. 58. 89-120 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pinzar,E.I., et.al.: "Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep."Proc.Natl.Acad.Sci.USA. 97. 4903-4907 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka,T. et.al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanaoka, Y., et.al.: "Structure and chromosomal localization of human and mouse genes for hematopoictic prostaglandin D synthasc."Eur.J.Biochem.. 267. 3315-3322 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pinzar, E.I., et.al.: "Structural basis of hematopoictic prostaglandin D synthase activity clucidated by site-directed mutagenesis."J.Biol.Chem.. 27. 31239-31244 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujimori, K., et.al.: "Transcriptinal activation of the human hematopoictic prostagalndin D synthase gene in megakaryoblastic cells."J.Biol.Chem.. 275 51. 40511-40516 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Urade, Y.and Hayaishi, O.: "Biochemical, structural, genetic, physiological, and pathophysiological featurcs of lipocalin-type prostaglandin D synthase."Biochim.Biophys.Acta. 1482. 259-271 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Urade, Y.and Hayaishi, O.: "Prostaglandin D synthase : structure and function."Vitamins and Hormones. 58. 89-120 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Pinzar, E.I., et.al.: "Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep."Proc.Natl.Acad.Sci.USA. 97. 4903-4907 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Matsuoka, T.et.al.: "Prostaglandin D_2 as a mediator of allergic asthma."Science. 287. 2013-2017 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kanaoka,Y., et.al.: "Structure and chromosomal localization of human and mouse genes for hematopoietic prostaglandin D synthase."Eur.J.Biochem.. 267. 3315-3322 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pinzar,E.I., et.al.: "Structural basis of hematopoietic prostaglandin D synthase activity elucidated by site-directed mutagenesis."J.Biol.Chem.. 27. 31239-31244 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujimori,K., et.al.: "Transcriptinal activation of the human hematopoietic prostagalndin D synthase gene in megakaryoblastic cells."J.Biol.Chem.. 275・51. 40511-40516 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Urade,Y.and Hayaishi,O.: "Biochemical, structural, genetic, physiological, and pathophysiological features of lipocalin-type prostaglandin D synthase."Biochim.Biopnys.Acta. 1482. 259-271 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Urade,Y.and Hayaishi,O.: "Prostaglandin D synthase : structure and function."Vitamins and Hormones. 58. 89-120 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Pinzar,E.I., et.al.: "Prostaglandin D synthase gene is involved in the regulation of non-rapid eye movement sleep."Proc.Natl.Acad.Sci.USA. 97. 4903-4907 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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