Regulation of airway smooth muscle -actin expression by glucocorticoids

Goldsmith AM, Hershenson MB, Wolbert MP, Bentley JK. Regulation of airway smooth muscle -actin expression by glucocorticoids. Am J Physiol Lung Cell Mol Physiol 292: L99–L106, 2007. First published September 15, 2006; doi:10.1152/ajplung.00269.2006.—Airway smooth muscle hypertrophy appears to be present in severe asthma. However, the effect of corticosteroids on airway smooth muscle cell size or contractile protein expression has not been studied. We examined the effects of dexamethasone, fluticasone, and salmeterol on contractile protein expression in transforming growth factor (TGF)-treated primary bronchial smooth muscle cells. Dexamethasone and fluticasone, but not salmeterol, each reduced expression of -smooth muscle actin and the short isoform of myosin light chain kinase. Steady-state -actin mRNA level and stability were unchanged, consistent with posttranscriptional control. Fluticasone significantly decreased -actin protein synthesis following treatment with the transcriptional inhibitor actinomycin D, indicative of an inhibitory effect on mRNA translation. Fluticasone also significantly increased -actin protein turnover. Finally, fluticasone reduced TGF-induced incorporation of -actin into filamentous actin, cell length, and cell shortening in response to ACh and KCl. We conclude that glucocorticoids reduce human airway smooth muscle -smooth muscle actin expression and incorporation into contractile filaments, as well as contractile function, in part by attenuation of mRNA translation and enhancement of protein degradation.