1. The beta-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells.
- Author
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Schnackenberg BJ, Jones SM, Pate C, Shank B, Sessions L, Pittman LM, Cornett LE, and Kurten RC
- 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
- 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.
- Published
- 2006
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