| Project/Area Number |
10470147
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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 | Tsukuba University (1999-2000)
Tohoku University (1998) |
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Principal Investigator |
SEKIZAWA Kiyohisa Tsukuba University, Clinical Medicine, Professor, 臨床医学系, 教授 (50171335)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | Oxidative stress / Airway inflammation / Airway epithelial cell / Bilirubin / Ferritin / Gene polymorphysm / Carbon monoxide / Pulmonary emphysema / ヘムオキシゲナーゼ / 気管支喘息 / 喫煙 / 肺胞マクロファージ |
|---|
| Research Abstract |
Heme oxygenase (HO) has been thought to degrade heme, but recently several investigations reveal that HO play an important role in oxidative stress response in body. The purpose of this study is to clarify role of HO-1, an inducible form of HO, in the respiratory system. In basic study, HO-1 is expressed in airway epithelial cells, vascular edothelial cells and alveolar macrophages. In the airway epithelial cells, HO-1 protects cells against hydrogen peroxide-induced injury through formation of bilirubin by degradation of heme. HO-1 also inhibits increases in vascular permeability during allergic inflammation of airways and supresses production of oxidant from alveolar macrophages. In clinical study, carbon monoxide produced during heme degradation by HO-1 increases in exhaled air of asthmatic patients and patients with upper respiratory tract infections, suggesting that oxidative stress contributes the pathophysiology of these diseases. Exhaled carbon monoxide reflects inflammation of asthmatic airway, and is useful in monitoring the control of asthma and the response to anti-inflammatory treatment in individual asthmatic patients. Furthermore, a (GT) n dinucleotide repeat in the 5'-flanking region of human HO-1 gene shows length polymorphism and modulates the level of gene transcription. The large size of a (GT) n repeat in the HO-1 gene promotor reduces HO-1 inducibility by reactive oxygen species in cigarette smoke, thereby resulting the development of pulmonary emphysema.
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