| Project/Area Number |
14570566
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Tokyo Women's Medical University |
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Principal Investigator |
TAMAOKI Jun Tokyo Women's Medical University, Department of Medicine, Assoc Prof, 医学部, 助教授 (60147395)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2003: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Beta2 receptor / Adrenaline / Airway remodeling / Airway epithelium / Cytokine / Epidermal growth factor / Salbutamol / Asthma / β2刺戟薬 / β2受容体 |
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| Research Abstract |
To determine whether β2-agonist affects airway epithelial cell proliferation in vivo and, if so, what the mechanism of action is, we examined the effect of salbutamol on the morphology of murine airways. SPF-SD rats were given aerosolized salbutamol using "flow-through" nose-only inhalation chambers at daily doses of 0.2-20μg for up to 6 weeks. Morphology of tracheal mucosa, labeling of epithelial cells with BrdU, and bronchial responsiveness were assessed. Exposure to salbutamol increased the thickness of tracheal epithelial layer and the number of BrdU-positive epithelial cells in a dose-and time-dependent manner, an effect that was inhibited by the EGFR inhibitor AG1478. In in vitro study with cultured airway epithelial cells, incubation with salbutamol stimulated protein and DNA syntheses and induced the expression of phosphorylated EGFR and its mRNA. These effects were reduced by specific inhibitors of HB-EGF and metalloproteinase. These results suggest that β2-agonist stimulates proliferation of airway epithelial cells and produces airway wall thickening via EGFR-dependent pathway, involving the release of metalloproteinase and the subsequent processing of HB-EGF.
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