| Project/Area Number |
13670596
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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 | NAGOYA UNIVERSITY |
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Principal Investigator |
HASEGAWA Yoshinori NAGOYA UNIVERSITY, UNIVERSITY HOSPITAL, ASSISTANT PROFESSOR, 医学部附属病院, 講師 (20270986)
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| Co-Investigator(Kenkyū-buntansha) |
KAWABE Tsutomu NAGOYA UNIVERSITY, UNIVERSITY HOSPITAL, MEDICAL STAFF, 医学部附属病院, 医員
SHIMOKATA Kaoru NAGOYA UNIVERSITY, GRADUATE SCHOOL OF MEDICINE, PROFESSOR, 大学院・医学系研究科, 教授 (10022906)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
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| Keywords | Bronchiolitis Obliterance / CD40 / Lipopolysaccharide / Gene deficient mice / Alveolar macrophages / CD40欠損マウス / マウスモデル / サイトカイン |
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| Research Abstract |
Cases of constrictive bronchiolitis obliterans (BO) have been reported involving patients with bone marrow transplants and heart/lung transplants as well as those with rheumatoid arthritis with or without penicillamine treatment. Although constrictive BO was a relatively rare disease, it has recently become the focus of renewed interest because the number of allograft recipients such as bone marrow and heart/lung transplants has been increasing. To investigate the pathogenesis of BO, we focused on the establishment of mouse experimental mode for BO and the role of CD40 molecule. When wild-type (WT) mice and CD40KO mice were injected intratracheally with LPS, LPS-induced lung injury was significantly reduced in CD40KO mice. Further, LPS-induced inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production was also inhibited in the lungs of CD40KO mice. In addition, the release of inflammatory mediators, that is, TNF-α, IL-1β, macrophage inflammatory protein 2 (MIP-2), reactive oxygen, nitrogen intermediates and MMP-9 into the bronchoalveolar lavage fluid, was significantly reduced in CD40KO mice. We studied the function of alveolar macrophages (AMφ) in each of mice ex vivo. Although iNOS in WT AMφ was induced in response to LPS, no iNOS expression could be detected in CD40KO AMφ. These results indicated that an absence of CD40 signaling followed by the decrease of the production of inflammatory mediators attenuated lung injury in uarine model. Our data suggest that the functional blockade of CD40 would yield one of the targets for the clinical treatment for lung injury including BO.
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