Submitted on May 31, 2005
Accepted on October 7, 2005
The 
-agonist isoproterenol attenuates EGF-stimulated wound closure in human airway epithelial cells
Bradley J Schnackenberg1*, Stacie M Jones2, Crystal Pate3, Brian Shank3, Laura Sessions3, Laura M Pittman3, Lawrence E Cornett4, and Richard C Kurten5
1 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
2 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
3 Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
4 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA
5 Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR, USA; Arkansas Children's Hospital Research Institute, Little Rock, AR, USA
* To whom correspondence should be addressed. E-mail: SchnackenbergBradley{at}uams.edu.
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 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 demonstrate that isoproterenol attenuates EGF-stimulated wound healing in 16HBE airway epithelial cell cultures. Through experiments with forskolin and cells overexpressing 2AR-YFP, 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.
