Increased airway smooth muscle (ASM) mass and contractility contribute to increased airway narrowing in asthma. The increased ASM mass may be caused by exposure to mitogens such as platelet-derived growth factor (PDGF) and extracellular matrix proteins such as collagen type I, which induce a proliferative, hypocontractile phenotype. Glucocorticosteroid and β2-adrenoceptor agonists are used in combination to treat asthma. This study investigated the impact of this combination on ASM hypocontractile phenotype in bovine tracheal smooth muscle. Glucocorticosteroids inhibited PDGF- and collagen I-induced proliferation and hypocontractility. When the glucocorticosteroid was combined with a β2-agonist, inhibition of the PDGF and collagen I effects occurred at 100-fold lower concentrations. These findings indicate that glucocorticosteroids and β2-adrenoceptor agonists synergistically inhibit ASM phenotype switching, which may contribute to the increased effectiveness of combined treatment in asthma.
See article at J Pharmacol Exp Ther 2012, 342:780–787.
- Copyright © 2012 by The American Society for Pharmacology and Experimental Therapeutics