Molecular mechanisms of airway mucus hypersecretion and airway clearance dynfunction induced by long-acting beta-2 agonist
| Project/Area Number |
23591127
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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 | Tokyo Women's Medical University |
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Principal Investigator |
TAMAOKI Jun 東京女子医科大学, 医学部, 教授 (60147395)
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| Project Period (FY) |
2011 – 2013
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
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| Keywords | 気道クリアランス / 粘液線毛輸送 / 気道上皮細胞 / 線毛運動 / β2受容体 / 気道上皮 / 細胞増殖 / 粘液分泌 / 喘息 / β２刺激薬 / リモデリング / 上皮成長因子受容体 / ERKカスケード / チロシンリン酸化 |
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| Research Abstract |
Stimulation of mouse tracheal epithelial cells with the long-acting beta-2 agonist salmeterol increased DNA and protein synthesis in a concentration-dependent manner, an effect that was abolished in the presence of a specific beta-2 receptor antagonist. Salmeterol also induced phosphorylation of EGFR and upregulated the expression of MUC5AC in cultured tracheal epithelial cells, and these effects were significantly inhibited by a EGFR tyrosine kinase inhibitor and transfection of dominant negative mutant of H-Ras, indicating that Ras-ERK cascade may be involved in the salmeterol-induced cell responses. Moreover, salmeterol increased mucociliary transport rate from the carina toward oropharynx in the mouse airway. Ciliary beat frequency of tracheal epithelial cells determined by a photoelectric method was increased in response to salmeterol. These findings suggest that simulation of airway epithelial cells with long-acting beta-2 agonist causes an improvement of airway clearance.
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Report
(4 results)
Research Products
(46 results)
