In vitro wounding of airway smooth muscle cell monolayers increases expression of TGF-beta receptors.

Abstract

During an exacerbation of asthma, there is bronchial epithelial cell injury and influx of inflammatory cells. In these instances, the release of proteases and various cytokines could lead to injury of the airway smooth muscle cells (ASMCs). Airway remodeling is a characteristic finding in asthma but the role of ASMC injury in remodeling is unknown. Previously, we demonstrated that mechanical wounding of confluent monolayers of bovine ASMCs resulted in the release of biologically active transforming growth factor-beta1 (TGF-beta1), which in turn, induced collagen I expression. In the present study, we demonstrate that after mechanical wounding, ASMCs had an increased expression of the signal transducing TGF-beta receptors TbetaR-I and TbetaR-II as detected by flow cytometry and Western analysis. Corticosteroids are standard therapy in asthma and the presence of dexamethasone decreased wound-induced release of TGF-beta1 and the expression of collagen I, fibronectin, and TbetaR-II. These results suggest that ASMC injury may play an important role in airway fibrosis mediated by TGF-beta1, which can be prevented by the use of corticosteroids.