Feeling the squeeze: does airway constriction stimulate the bronchial epithelium?

Bronchospasm is a frequent occurrence in the airways of asthmatics, and subjects the bronchial epithelium to compressive stress. We show here that compressive stresses similar to those occurring in vivo trigger human bronchial epithelial cells to release endothelin (ET) and transforming growth factor-/spl beta/2 (TGF-/spl beta/2). Compressive stress leads to an increase in the steady state level of mRNA for both ET-1 and ET-2, and to the release of TGF-/spl beta/2 from a pre-formed, cell-associated pool. We also show that ET-2 and TGF-/spl beta/2 stimulate fibrotic protein synthesis by human lung fibroblasts, and act synergistically in combination. Our results demonstrate that compressive stress elicits selective release of fibrotic mediators from bronchial epithelium, indicating that bronchospasm may contribute to the subepithelial fibrosis and airways remodeling that characterize asthma.