Dexamethasone and salbutamol stimulate human lung fibroblast proliferation

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

פרסום מחקרי: פרסום בכתב עתמאמרביקורת עמיתים

תקציר

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 β2-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 [3H]-Thymidine was added (24 h) to measure their proliferation. IL-6 production in the supernatants of confluent monolayers 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 β2-bronchodilators and inhaled glucocorticosteroids on the natural history of asthma.

שפה מקוריתאנגלית אמריקאית
עמודים (מ-עד)249-256
מספר עמודים8
כתב עתWorld Allergy Organization Journal
כרך4
מספר גיליון12
מזהי עצם דיגיטלי (DOIs)
סטטוס פרסוםפורסם - דצמ׳ 2011

ASJC Scopus subject areas

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  • ???subjectarea.asjc.2400.2403???
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