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The beta-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells.
- Source :
-
American journal of physiology. Lung cellular and molecular physiology [Am J Physiol Lung Cell Mol Physiol] 2006 Mar; Vol. 290 (3), pp. L485-91. Date of Electronic Publication: 2005 Oct 14. - Publication Year :
- 2006
-
Abstract
- Asthma is a disease characterized by reversible airway obstruction. An additional hallmark of chronic asthma is altered wound healing that leads to airway remodeling. Although beta-agonists are effective in treating the bronchospasm associated with asthma, their effects on airway wound healing, which are related to airway remodeling, are unknown. It has been demonstrated that beta-agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the beta-agonist isoproterenol would affect wound healing. Using an in vitro scrape wound assay, we demonstrated that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing beta2-adrenergic receptor-yellow fluorescent protein, we show that attenuation is due to the accumulation of cAMP and the involvement of at least one additional pathway. Furthermore, attenuation is not due to a direct effect on the EGF receptor or to an alteration of the ERK/MAPK signaling cascade. Based on these results, we propose that isoproterenol may exert its effects through other MAPK signaling pathways (JNK and/or p38) or through parallel mechanisms. These results also demonstrate a problem of potential therapeutic relevance in which a commonly prescribed medication may alter wound healing and contribute to the remodeling of asthmatic airways.
- Subjects :
- Bacterial Proteins genetics
Bacterial Proteins metabolism
Bronchi cytology
Bronchi metabolism
Cells, Cultured
Colforsin pharmacology
Cyclic AMP metabolism
Drug Combinations
Epithelial Cells metabolism
ErbB Receptors metabolism
Humans
Luminescent Proteins genetics
Luminescent Proteins metabolism
Mitogen-Activated Protein Kinases metabolism
Receptors, Adrenergic, beta-2 genetics
Receptors, Adrenergic, beta-2 metabolism
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
Signal Transduction
Adrenergic beta-Agonists pharmacology
Bronchi drug effects
Epidermal Growth Factor pharmacology
Epithelial Cells drug effects
Isoproterenol pharmacology
Wound Healing drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1040-0605
- Volume :
- 290
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- American journal of physiology. Lung cellular and molecular physiology
- Publication Type :
- Academic Journal
- Accession number :
- 16227322
- Full Text :
- https://doi.org/10.1152/ajplung.00233.2005