The beta-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells |
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Authors: | Schnackenberg Bradley J Jones Stacie M Pate Crystal Shank Brian Sessions Laura Pittman Laura M Cornett Lawrence E Kurten Richard C |
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Affiliation: | Dept. of Pediatrics, Univ. of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, 1120 Marshall St., Slot 512-13, Little Rock, AR 72202, USA. SchnackenbergBradley@uams.edu |
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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. |
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