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Molecular mechanisms underlying ARDS and development of novel therapeutic strategies using genetically-engineered mice

Research Project

Project/Area Number 12470134
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Respiratory organ internal medicine
Research InstitutionThe University of Tokyo

Principal Investigator

NAGASE Takahide  Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (40208004)

Co-Investigator(Kenkyū-buntansha) UOZUMI Naonori  Faculty of Medicine, Research Associate, 大学院・医学系研究科, 助手 (70313096)
YOKOMIZO Takehiko  Faculty of Medicine, Associate Professor, 大学院・医学系研究科, 助教授 (60302840)
KURIHARA Hiroki  Kumamoto University, Institute of Molecular Embryology and Genetics, Professor, 発生医学研究センター, 教授 (20221947)
ISHII Satoshi  Faculty of Medicine, Research Associate, 大学院・医学系研究科, 助手 (10300815)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥15,800,000 (Direct Cost: ¥15,800,000)
Fiscal Year 2002: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2001: ¥4,900,000 (Direct Cost: ¥4,900,000)
Fiscal Year 2000: ¥6,000,000 (Direct Cost: ¥6,000,000)
KeywordsPAF / ARDS / Knockout mouse / Transgenic mouse / LPS / CGRP / PAF / ARDS / Knockout mouse / Transgenic mouse / LPS / CGRP
Research Abstract

Adult respiratory distress syndrome (ARDS) is an acute lung injury and the mortality rate for ARDS ranges from 40-70% despite of intensive care using currently available drugs. However, its mechanism still remains to be elucidated. Platelet-activating factor (PAF) and eicosanoids are lipid mediators that have various biological effects. The purpose of this study is to investigate the role of PAF and cPLA_2 in lung inflammatory diseases using genetically-engineered mice. To address this question, we used mutant mice, which were established in our laboratory, i.e., PAFR transgenic mice, PAFR gene-disrupted mice, and cPLA_2 gene-disrupted mice. Our observations suggest that both PAF and cPLA_2 are involved in the pathogenesis of acute lung injury and that the inhibition of these pathways might provide a novel therapeutic approach to ARDS.

Report

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

    (21 results)

All Other

All Publications (21 results)

  • [Publications] Nagase T et al.: "Acute lung injury by sepsis and acid aspiration : a key role for cytosolic phospholipase A_2"Nature Immunol. 1. 42-46 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al.: "Airway hyperresponsiveness in transgenic mice overexpressing platelet-activatin factor receptor is mediated by an atropine sensitive pathway"Am J Respir Crit Care Med. 165. 200-205 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al.: "A pivotal role of cytosolic phospholipase A_2 in bleomycin-induced pulmonary fibrosis"Nature Med. 8. 480-484 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki-Nagase T, Nagase T et al.: "Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice"Am J Physiol Lung Cell Mol Physiol. 283. L963-L970 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii S, Nagase T et al.: "Platelet-activating factor receptor"Prostaglandins Other Lipid Mediat. 68. 599-609 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al.: "A potent inhibitor of cytosolic phospholipase A_2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice"Am J Physiol Lung Cell Mol Physiol. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T, Uozumi N, Ishii S, Kume K, Izumi T, Ouchi Y, Shimizu T.: "Acute lung injury by sepsis and acid aspiration : a key role for cytosolic phospholipase A_2"Nature Immunol. 1. 42-46 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T, Ishii S, Shindou H, Ouchi Y, Shimizu T.: "Airway hyperresponsiveness in transgenic mice overexpressing platelet-activating factor receptor is mediated by an atropine sensitive pathway"Am J Respir Crit Care Med. 165. 200-205 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T, Uozumi N, Ishii S, Kita Y, Yamamoto H, Ohga E, Ouchi Y, Shimizu T.: "A pivotal role of cytosolic phospholipase A_2 in bleomycin-induced pulmonary fibrosis"Nature Med. 8. 480-484 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Aoki-Nagase T, Nagase T, Oh-hashi Y, Shindo T, Kurihara Y, Yamaguchi Y, Yamamoto H, Tomita T, Ohga E, Nagai R, Kurihara H, Ouchi Y.: "Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice"Am J Physiol Lung Cell Mol Physiol. 283. L963-L970 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishii S, Nagase T, Shimizu T.: "Platelet-activating factor receptor"Prostaglandins Other Lipid Mediat. 68. 599-609 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T, Uozumi N, Aoki-Nagase T, Terawaki K, Ishii S, Tomita T, Yamamoto H, Hashizume K, Ouchi Y, Shimizu T.: "A potent inhibitor of cytosolic phospholipase A_2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice"Am J Physiol Lung Cell Mol Physiol, published on line, 10.1152/ajplung.00396. in press. (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Nagase T et al.: "Acute lung injury by sepsis and acid aspiration : a key role for cytosolic phospholipase A_2"Nature Immunol. 1. 42-46 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagase T et al.: "Airway hyperresponsiveness in transgenic mice overexpressing platelet-activatin factor receptor is mediated by an atropine sensitive pathway"Am J Respir Crit Care Med. 165. 200-205 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagase T et al.: "A pivotal role of cytosolic phospholipase A_2 in bleomycin-induced pulmonary fibrosis"Nature Med. 8. 480-484 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Aoki-Nagase T, Nagase T et al.: "Attenuation of antigen-induced airway hyperresponsiveness in CGRP-deficient mice"Am J Physiol Lung Cell Mol Physiol. 283. L963-L970 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishii S, Nagase T et al.: "Platelet activating factor receptor"Prostaglandins Other Lipid Mediat. 68. 599-609 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Nagase T et al.: "A potent inhibitor of cytosolic phospholipase A_2, arachidonyl trifluoromethyl ketone, attenuates LPS-induced lung injury in mice"Am J Physiol Lung Cell Mol Physiol. (in press).

    • Related Report
      2002 Annual Research Report
  • [Publications] T.Nagase, et al.: "Airway hyperresponsiveness in transgenic mice overexpressing platelet activating factor receptor is mediated by an atropine-sensitive pathway"Am J Respir Crit Care Med. 165. 200-205 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Yamaguchi, S.fukuhara, T.Nagase, et al.: "A novel mouse β-defensin, mBD-6, predominantly expressed in skeletal muscle"J Biol Chem. 276. 31510-31514 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T.Nagase et al: "Acute lung injury by sepsis and acid aspiration : a key role for cytosolic phospholipase A_<>"Nature Immunology. Vol.1・1. 42-46 (2000)

    • Related Report
      2000 Annual Research Report

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

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