Dexamethasone and salbutamol stimulate human lung fibroblast proliferation (original) (raw)

2011, The World Allergy Organization journal

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. In this study, we aimed to investigate the direct effect of the drugs most frequently used in asthma, that is, glucocorticosteroids (dexamethasone) and shortacting β(2)-agonists (salbutamol), on human lung fibroblast proliferation when unstimulated or activated by mast cells or eotaxin. Subconfluent human fetal lung or bronchial fibroblasts were incubated with different concentrations of the drugs (24 h) 6 activators, and [(3)H]-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 ...

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Fluticasone and salmeterol downregulatein vitro, fibroblast proliferation and ICAM-1 or H-CAM expression

European Respiratory Journal, 2001

β2-adrenoreceptor agonists have pharmacological properties that may suggest an inhibitory effect on various aspects of the inflammatory and repair processes that characterize asthma.Since fibroblasts express β2-adrenoreceptors, the effects of different concentrations (0.1–100 nM) of fluticasone propionate (FP), salmeterol (S) and their combination (FP+S) on lung fibroblast proliferation and adhesion molecule expression were evaluated.Stimulation of human foetal lung fibroblasts with a fibrogenic cytokine, basic fibroblast growth factor (bFGF), resulted in a [methyl-3H] thymidine ([3H]TdR) uptake, four-fold higher than that of control cultures (p=0.0001) and was significantly inhibited by S, at all the concentrations tested (0.1–100 nM; p<0.05). No changes in bFGF-induced cell proliferation were observed in the presence of FP (0.1–100 nM; p>0.05, all comparisons). In addition, the association FP+S did not improve the inhibitory activity of S alone (p>0.05, each comparison). ...

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Dexamethasone regulation of lung epithelial cell and fibroblast interleukin-11 production

American Journal of Physiology-Lung Cellular and Molecular Physiology, 1999

Studies were undertaken to define the effects of corticosteroids on stromal cell interleukin (IL)-11 production. Unstimulated A549 epithelial-like cells produced modest amounts of IL-11, and transforming growth factor (TGF)-β1 was a potent, dose-dependent stimulator of A549 cell IL-11 elaboration. Dexamethasone inhibited the levels of basal and TGF-β1-stimulated IL-11 elaboration in a dose-dependent fashion. In the setting of TGF-β1 stimulation, dexamethasone caused a >90% decrease in IL-11 production at 10−6 M, a 50% decrease in IL-11 production at ∼1 × 10−9 M, and significant inhibition at 10−10 M. This dexamethasone-induced inhibition was reversed by the glucocorticoid-receptor antagonist RU-486. Dexamethasone also inhibited respiratory syncytial virus, rhinovirus, and TGF-β1-stimulated IL-11 production by MRC-5 lung fibroblasts. In all cases, dexamethasone caused comparable changes in IL-11 mRNA accumulation. Nuclear run-on studies demonstrated that dexamethasone caused a mod...

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Reduced suppressive effect of β2-adrenoceptor agonist on fibrocyte function in severe asthma

Respiratory research, 2017

Patients with severe asthma have increased airway remodelling and elevated numbers of circulating fibrocytes with enhanced myofibroblastic differentiation capacity, despite being treated with high doses of corticosteroids, and long acting β2-adrenergic receptor (AR) agonists (LABAs). We determined the effect of β2-AR agonists, alone or in combination with corticosteroids, on fibrocyte function. Non-adherent non-T cells from peripheral blood mononuclear cells isolated from healthy subjects and patients with non-severe or severe asthma were treated with the β2-AR agonist, salmeterol, in the presence or absence of the corticosteroid dexamethasone. The number of fibrocytes (collagen I+/CD45+ cells) and differentiating fibrocytes (α-smooth muscle actin+ cells), and the expression of CC chemokine receptor 7 and of β2-AR were determined using flow cytometry. The role of cyclic adenosine monophosphate (cAMP) was elucidated using the cAMP analogue 8-bromoadenosine 3',5'-cyclic monoph...

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