The effect of enantiomers of beta-agonists on myofibroblast-derived vascular endothelial growth factor and other matrix components in the presence of dust-mite extract

Abstract

Beta(2)-adrenergic receptor agonists have been shown to modulate airway epithelial cell and smooth muscle release of cytokines and growth factors transforming growth factor (TGF) beta, associated with remodeling, is known to up-regulate the synthesis of vascular endothelial growth factor (VEGF) and stimulate differentiation of fibroblasts to the myofibroblast phenotype. VEGF and fibronectin can promote angiogenesis and (S)-albuterol can induce VEGF secretion from normal human lung fibroblasts (NHLF). We hypothesize that (S)-albuterol could stimulate myofibroblast secretion and expression of VEGF and fibronectin in the presence of Dermatophagoides pteronyssinus extract. Cultured NHLFs were stimulated with IL-1beta, TGF-beta, D. pteronyssinus, and treated with (R)- and (S)-enantiomers of albuterol. VEGF and fibronectin and basic fibroblast growth factor (bFGF) were measured by ELISA and mRNA. VEGF secretion by fibroblasts was twofold higher with 10(-7) M of (R) relative to (S) (p < 0.05). Myofibroblast secretion of VEGF was increased twofold over fibroblasts, but there was no difference between enantiomers. (S)-albuterol at 10(-8)-10(-4) M caused an increase in VEGF mRNA that paralleled VEGF secretion relative to 10(-8)-10(-4) M. Fibronection secretion by myofibroblasts but not fibroblasts was increased by 10(-5) M of (S) relative to (R) in the presence of recombinant interleukin 1 (rhIL-1)beta and D. pteronyssinus (S)-albuterol at 10(-6) M increased bFGF. The 10(-6) M of (S)-albuterol, but not (R)-albuterol, may promote angiogenesis. Increased fibronectin or bFGF by (S)-albuterol could enhance matrix deposition and remodeling in a subset of asthmatic patients.