Dexamethasone and Salbutamol Stimulate Human Lung Fibroblast ProliferationReport as inadecuate




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World Allergy Organization Journal

, Volume 4, Issue 12, pp 249–256

First Online: 14 December 2011

Abstract

BackgroundAsthma 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.

ObjectiveIn this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids dexamethasone and shortacting β2-agonists salbutamol, on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin.

MethodsSubconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs 24 h 6 activators, and 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.

ResultsBoth 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.

ConclusionsThese observations if corroborated by in vivo data may possibly account for the deleterious effect of long-term therapy with β2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.

Keywordsfibroblasts lung proliferation dexamethasone salbutamol IL-6  Download fulltext PDF



Author: Eran Pickholtz - Dan Admon - Uzi Izhar - Neville Berkman - Francesca Levi-Schaffer

Source: https://link.springer.com/







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