1. The [beta]-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells
- Author
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Schnackenberg, Bradley J., Jones, Stacie M., Pate, Crystal, Shank, Brian, Sessions, Laura, Pittman, Laura M., Cornett, Lawrence E., and Kurten, Richard C.
- Subjects
Bronchial spasm -- Research ,Asthma -- Research ,Asthma -- Health aspects ,Epinephrine -- Receptors ,Epinephrine -- Research ,Epinephrine -- Health aspects ,Biological sciences - 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 [[beta].sub.2]-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. [[beta].sub.2]-adrenergic receptor; epidermal growth factor receptor; asthma; bronchospasm
- Published
- 2006