Decreases in airway epithelial wound healing following β‐adrenergic receptor activation involves inhibition of CFTR

Abstract

Blocking CFTR channel activity or silencing expression by RNA interference produces a significant delay in wound healing by impeding lamellipodia protrusion and reducing the rate of cell migration into the wound. The objective of this study was to investigate a possible role for CFTR in β-adrenergic receptor mediated inhibition of human bronchial epithelial (HBE) cell migration and wound repair. HBE cells were grown to confluence on impedance sensing chamber arrays, each containing a circular 250 μm diameter electrode. Wound repair was monitored by continuously applying alternating current (~1 μA, 15 kHz) and measuring increases in impedance as cells migrated onto the electrode surface. As wound closure proceeded and more cells covered the electrode, impedance increased until reaching a plateau when wound closure was complete. Exposure to 10 μM epinephrine produced a significant delay in wound closure from 4.1 hrs to 7.6 hrs. Pretreatment with the β-adrenergic receptor antagonist propranolol (10 μM) abolished the inhibitory effects of epinephrine. Moreover, inhibition of CFTR activity by addition of 20 μM CFTRinh-172 also blocked the effects of epinephrine on cell migration and wound repair. These results demonstrate that bronchial epithelial wound healing is significantly reduced following exposure to β-adrenergic receptor agonists and that this effect involves inhibition of CFTR channel activity.