Abstract
Background: Mucosal inflammation, thickening of the basement membrane and increased mass of airway smooth muscle influence asthma airway remodeling. Different cell types contribute to extracellular matrix deposition. Airway smooth muscle cells (ASMC) not only contract and relax but also proliferate, respond to inflammatory stimuli and produce extracellular matrix. As shown previously, glucocorticoids increase the deposition of extracellular matrix by human ASMC under inflammatory conditions.
Methods: To analyse the effect of the β2-agonist formoterol on glucocorticoid-induced extracellular matrix deposition, primary ASMC cultures were set up from asthmatics and non-asthmatic controls. Confluent cells were stimulated with 5% serum with or without a single drug or a combination for a further 72 hr with [3H] proline (0.5microCi). Total extracellular matrix and collagen deposition were monitored by scintillation counts, described earlier.
Results: Compared to non-stimulated cells 5% serum increased matrix and collagen deposition by +42% which was further increased in the presence of 10-8 M glucocorticoids (dexamethasone: +86%, budesonide: +66%, beclomethasone: +59%, fluticasone: +55%). However, 10-8 M formoterol reduced serum-induced matrix and collagen deposition by 36%. In combination, formoterol abolished the stimulating effect of glucocorticoids on matrix and collagen deposition and reduced matrix deposition. This was dose-dependent.
Conclusions: Our data show that β2-agonists combined with glucocorticoids reduce the excessive matrix deposition induced by glucocorticoids alone. Thus, combination therapy may exhibit benefits for asthmatic patients beyond bronchodilating and anti-inflammatory effects.
- © 2011 ERS