| Project/Area Number |
26461189
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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 |
Respiratory organ internal medicine
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| Research Institution | Okayama University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
宮原 信明 岡山大学, 保健学研究科, 教授 (70335610)
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| Project Period (FY) |
2014-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 気管支喘息 / 肺気腫 / COPD / 好酸球性気道炎症 / 好中球性気道炎症 / レチノイドX受容体 / レチノイドX受容体パーシャルアゴニスト / 核内受容体 / 気道炎症 / アレルギー性気道炎症 / パーシャルアゴニスト / RXR選択的アゴニスト |
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| Outline of Final Research Achievements |
Oral administration of a novel Retinoid X receptor (RXR) partial agonist (NEt-4IB) significantly suppressed airway hyperresponsiveness, inflammatory cell accumulation in the airways, and attenuated the levels of TNF-α in the lung, and IL-5, IL-13 and NO levels in bronchoalveolar lavage fluid, and goblet cells hyperplasia and NF-κB expression in lung tissue in a murine model of asthma. Furthermore, in a porcine pancreas elastase (PPE)- and cigarette smoke extract (CSE)-induced emphysema model, treatment with NEt-4IB significantly suppressed the emphysematous changes and neutrophilic airway inflammation, proteinase/anti-proteinase imbalance, and increased anti-oxidant activity. These data suggest that RXRs may play crucial roles in the mechanism of airway inflammation, airway hyperresponsiveness, and emphysematous change, and the novel RXR partial agonist NEt-4IB may be a promising candidate for the treatment of asthma and COPD.
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