| Project/Area Number |
14570544
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 |
YAMAMOTO Hiroshi (2003) The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (10361487)
大賀 栄次郎 (2002) 東京大学, 医学部附属病院, 助手 (00323577)
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| Co-Investigator(Kenkyū-buntansha) |
TOMIYA Tetsuji The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 教務職員 (50345203)
SHINDO Takayuki The Univ. of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (90345215)
NAGASE Takahide The Univ. of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (40208004)
山本 寛 東京大学, 医学部附属病院, 医員
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Keywords | CGRP / Bronchial asthma / Airway heperresponsiveness / Knockout mouse / ノックアウトマウス / 気道過敏 |
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| Research Abstract |
Bronchial hyperresponsiveness and eosinophilia are major characteristics of asthma. Calcitonin gene-related peptide (CGRP) is a neuropeptide that has various biological actions. In the current study, we questioned whether CGRP might have pathophysiological roles in airway hyperresponsiveness and eosinophilia in asthma. To determine the exact roles of endogenous CGRP in vivo, we chose to study antigen-induced airway responses using CGRP gene-disrupted mice. After ovalbumin sensitization and antigen challenge, we assessed airway responsiveness and measured proinflammatory mediators. In the sensitized CGRP gene-disrupted mice, antigen-induced bronchial hyperresponsiveness was significantly attenuated compared to the sensitized wild type mice. Antigen challenge induced eosinophil infiltration in bronchoalveolar lavage fluid (BALF), whereas no differences were observed between the wild type and CGRP mutant mice. Antigen-induced increases in cysteinyl leukotriene production in the lung was significantly reduced in the CGRP-disrupted mice. These findings suggest that CGRP could be involved in the antigen-induced airway hyperresponsiveness, but not eosinophil infiltration, in mice. The CGRP mutant mice may provide appropriate models to study molecular mechanisms underlying CGRP-related diseases.
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