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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

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Beta2-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.
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Keywords: (S)-albuterol; VEGF; beta-agonists; beta2-adrenergic receptor agonists; enantiomers; endothelial growth factor; fibroblasts

Document Type: Research Article

Affiliations: Division of Allergy Immunology and Clinical Immunopathology, Departments of Medicine and Pathology, Nassau University Medical Center, an affiliate of North Shore Long Island Jewish Health Care Systems and the State University of New York at Stony Brook, Stony Brook, New York

Publication date: 2008-03-01

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  • Allergy and Asthma Proceedings is a peer reviewed publication dedicated to distributing timely scientific research regarding advancements in the knowledge and practice of allergy, asthma and immunology. Its primary readership consists of allergists and pulmonologists.

    The goal of the Proceedings is to publish articles with a predominantly clinical focus which directly impact quality of care for patients with allergic disease and asthma.

    Featured topics include asthma, rhinitis, sinusitis, food allergies, allergic skin diseases, diagnostic techniques, allergens, and treatment modalities. Published material includes peer-reviewed original research, clinical trials and review articles.

    Articles marked "F" offer free full text for personal noncommercial use only.

    The journal is indexed in Thomson Reuters Web of Science and Science Citation Index Expanded, plus the National Library of Medicine's PubMed service.
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