2013 Fiscal Year Final Research Report
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 |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Tokyo Women's Medical University |
Principal Investigator |
TAMAOKI Jun 東京女子医科大学, 医学部, 教授 (60147395)
|
Project Period (FY) |
2011 – 2013
|
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 |
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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Research Products
(31 results)