| Project/Area Number |
24591467
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
膠原病・アレルギー・感染症内科学
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| Research Institution | Teikyo University (2014)
Saga University (2012-2013) |
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Principal Investigator |
SUZUKI SHOICHI 帝京大学, 医療共通教育研究センター, 講師 (40253695)
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| Co-Investigator(Kenkyū-buntansha) |
IZUHARA Kenji 佐賀大学, 医学部, 教授 (00270463)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2012: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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| Keywords | 気管支喘息 / ペルオキシダーゼ / ヒポチオシアン酸 / ペンドリン / 気道上皮細胞 / 喘息 / ヒポチオシアン酸イオン |
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| Outline of Final Research Achievements |
In this study, we first examined effects of hypothiocyanite (OSCN-) on airway epithelial cells using in vitro OSCN- production system. Next we examine asthma pathogenesis of the individual knockout mice of three kinds of heme-peroxidases, LPO, MPO, EPO, which catalyze thiocyanate to produce OSCN-. Finally we checked effects of methimazole, an inhibitor of all heme-peroxidases on airway inflammation. Here we showed that OSCN- in low doses was sensed by protein kinase A followed by activation of NF-kB in the airway epithelial cells, whereas OSCN- in high doses induced necrotic cell death. One defect of the three kinds of heme-peroxidases showed no dramatic alleviation of asthma pathogenesis, however, inhibition of all the heme-peroxidases with methimazole improved airway inflammation. Our data strongly suggest that inhibition of heme-peroxidase is a novel therapeutic strategy for asthma.
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