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This Article Full Text Full Text (PDF) All Versions of this Article: 290/3/L485    most recent 00233.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Schnackenberg, B. J. Articles by Kurten, R. C. Search for Related Content PubMed PubMed Citation Articles by Schnackenberg, B. J. Articles by Kurten, R. C.

The -agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells

Departments of ¹Pediatrics and ²Physiology and Biophysics, University of Arkansas for Medical Sciences, and ³Arkansas Children's Hospital Research Institute, Little Rock, Arkansas

Submitted 31 May 2005 ; accepted in final form 7 October 2005

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 -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 -agonists can alter the signaling of epidermal growth factor (EGF) receptors, which are important in timely wound healing. Therefore, we hypothesized that the -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 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.

₂-adrenergic receptor; epidermal growth factor receptor; asthma; bronchospasm