2002 Fiscal Year Final Research Report Summary
Molecular mechanisms underlying ARDS and development of novel therapeutic strategies using genetically-engineered mice
| Project/Area Number |
12470134
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
NAGASE Takahide Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (40208004)
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| 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)
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| Project Period (FY) |
2000 – 2002
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| Keywords | PAF / ARDS / Knockout mouse / Transgenic mouse / LPS / CGRP |
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| 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.
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[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
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[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
