Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts

Spoelstra, FM; Postma, D.S.; Hovenga, H; Noordhoek, JA; Kauffman, Hf

doi:10.1183/09031936.00.15106800

Cited by 38 publications

(20 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, at the two highest concentrations tested, S significantly increased the inhibitory activity of FP alone on ICAM-1 expression. These findings are in agreement with the results of a recent report, showing inhibition of ICAM-1 expression by human lung fibroblast primary cultures in the presence of budesonide and formoterol [31]. Indeed, b 2 -adrenergic receptor agonists may also activate glucocorticoid receptors in primary human lung fibroblasts [32].…”

Section: Discussionsupporting

confidence: 83%

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

Silvestri¹,

Fregonese²,

Sabatini³

et al. 2001

Eur Respir J

View full text Add to dashboard Cite

b 2 -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 b 2 -adrenoreceptors, the effects of different concentrations (0.1 -100 nM) of fluticasone propionate (FP), salmeterol (S) and their combination (FPzS) 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-3 H] thymidine ([ 3 H]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; pv0.05). No changes in bFGFinduced cell proliferation were observed in the presence of FP (0.1 -100 nM; pw0.05, all comparisons). In addition, the association FPzS did not improve the inhibitory activity of S alone (pw0.05, each comparison). An upregulation of intercellular adhesion molecule-1 (ICAM-1) expression was induced by tumour necrosis factor-a (TNF-a) (p~0.0004), but not by interleukin-4 (IL-4) (pw0.05), while none of the two cytokines were able to increase hyaluronic-cellular adhesion molecule (H-CAM) expression by lung fibroblasts (pw0.05). A significant downregulation of ICAM-1 or H-CAM expression was demonstrated in the presence of FP or S, at all concentrations tested (0.1 -100 nM; pv0.01, each comparison). Interestingly, S (10 nM and 100 nM) was able to enhance the inhibitory activity of FP on ICAM-1 expression (pv0.01), but not on H-CAM expression (pw0.1).These results show that in human foetal lung fibroblasts, fluticasone propionate and salmeterol are effective in modulating in vitro, different lung fibroblast biological functions that are likely to be involved in airway remodelling.

show abstract

Section: Discussionsupporting

confidence: 83%

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

Silvestri¹,

Fregonese²,

Sabatini³

et al. 2001

Eur Respir J

View full text Add to dashboard Cite

show abstract

“…However, for reducing GM-CSF, the effects of budesonide and the b 2 -agonist are largely additive. This is in concordance with recent results of studies performed using human lung fibroblasts, in which budesonide and formoterol strongly blunted the IL-1b induced secretion of GM-CSF and intracellular adhesion molecule-1 (ICAM-1) [26]. In the pulse experiments, the combination of budesonide and formoterol had the preference of giving a GM-CSF block with less variance, but there was less strong support for an additive efficacy.…”

Section: Discussionsupporting

confidence: 79%

Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells

2001

View full text Add to dashboard Cite

The effect of formoterol, alone and in combination with budesonide, upon tumour necrosis factor-a stimulated (10 ng?mL -1 ) human bronchial epithelial cells was investigated.Addition of formoterol (¢10 -10 M) reduced granulocyte macrophage-colony stimulating factor (GM-CSF) levels, as assessed by enzyme-linked immunosorbent assay, by 40 -50% and increased interleukin (IL)-8 levels by y50%. The effects of formoterol were long lasting (23 h). Budesonide (10 -8 M) reduced the amounts of both cytokines (GM-CSF and IL-8) by 40%. Simultaneous addition of formoterol and budesonide reduced GM-CSF levels y75%, while IL-8 levels were decreased y40%, similar to the reduction obtained with budesonide alone. The glucocorticoid receptor (GR) antagonist RU486 did not influence the effect of formoterol, suggesting no involvement of the GR. Formoterol rapidly induced an elevation in intracellular cyclic adenosine monophosphate, which was reduced in the presence of propranolol. In addition, the alterations in cytokine secretion induced by formoterol could be fully blocked by propranolol, demonstrating that these effects are b 2 -receptor mediated.In conclusion, the combination of budesonide and formoterol reduces the secretion of granulocyte macrophage-colony stimulating factor to basal levels and counteracts the capacity of formoterol alone to induce interleukin-8 production, modulations which may facilitate improved asthma control.

show abstract

“…The identity of other fibroblast ligands has not been determined, but apparently, it reportedly does not involve extracellular matrix proteins or blood proteins since PMA-mediated neutrophil adhesion to lung fibroblasts does not require serum, albumin, type I or type IV collagen, or fibronectin (235). More recently, it has become apparent that cytokines and mast cell products will induce VCAM-1 expression on human lung fibroblasts (172,230,246). While ␤ 1 -integrins ␣ 4 and ␣ 9 are known to bind VCAM-1 (230,257), it remains to be determined whether VCAM-1 expression on lung fibroblasts mediates ␣ 4 -and ␣ 9 -dependent neutrophil adhesion and motility.…”

Section: Fibroblasts: a Source Of Contact Guidance And Stimulatiomentioning

confidence: 99%

Unique Structural Features That Influence Neutrophil Emigration Into the Lung

Burns

Smith²,

Walker³

2003

Physiological Reviews

267

273

View full text Add to dashboard Cite

Neutrophil emigration in the lung differs substantially from that in systemic vascular beds where extravasation occurs primarily through postcapillary venules. Migration into the alveolus occurs directly from alveolar capillaries and appears to progress through a sequence of steps uniquely influenced by the cellular anatomy and organization of the alveolar wall. The cascade of adhesive and stimulatory events so critical to the extravasation of neutrophils from postcapillary venules in many tissues is not evident in this setting. Compelling evidence exists for unique cascades of biophysical, adhesive, stimulatory, and guidance factors that arrest neutrophils in the alveolar capillary bed and direct their movement through the endothelium, interstitial space, and alveolar epithelium. A prominent path accessible to the neutrophil appears to be determined by the structural interactions of endothelial cells, interstitial fibroblasts, as well as type I and type II alveolar epithelial cells.

show abstract

Budesonide and formoterol inhibit ICAM-1 and VCAM-1 expression of human lung fibroblasts

Cited by 38 publications

References 39 publications

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

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

Effects of formoterol and budesonide on GM-CSF and IL-8 secretion by triggered human bronchial epithelial cells

Unique Structural Features That Influence Neutrophil Emigration Into the Lung

Contact Info

Product

Resources

About