Dexamethasone and salbutamol stimulate human lung fibroblast proliferation

Background Asthma is characterized by bronchial hyperreactivity and airway remodeling. Subepithelial fibrosis, a feature of remodeling, is accompanied by activation of fibroblasts to myofibroblasts, with excessive proliferation and increased collagen, extracellular matrix protein, and profibrogenic...

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Bibliographic Details
Published in:The World Allergy Organization journal 2011-12, Vol.4 (12), p.249
Main Authors: Pickholtz, Eran, Admon, Dan, Izhar, Uzi, Berkman, Neville, Levi-Schaffer, Francesca
Format: Article
Language:English
Subjects:
Albuterol
Asthma
Care and treatment
Cell proliferation
Dexamethasone
Dosage and administration
Drug therapy
Fibroblasts
Health aspects
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Summary:Background Asthma is characterized by bronchial hyperreactivity and airway remodeling. Subepithelial fibrosis, a feature of remodeling, is accompanied by activation of fibroblasts to myofibroblasts, with excessive proliferation and increased collagen, extracellular matrix protein, and profibrogenic cytokine production. Mast cells are important in the development of asthma and its fibrotic changes. Objective In this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting [beta]2-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin. Methods Subconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [.sup.3.sup.H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent mono-layers cultured in the presence of the drugs or forskolin (24 h) was analyzed by enzyme-linked immunosorbent assay. Results Both drugs alone and in the presence of the activators enhanced fibroblast proliferation in a seemingly synergistic way for both fetal and bronchial fibroblasts. Dexamethasone was found to decrease IL-6 production, while salbutamol increased it. Conclusions These observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with [beta]2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.
ISSN:1939-4551
1939-4551
DOI:10.1097/WOX.0b013e31821d1186