The expression of intercellular adhesion molecule-1 and the beta 1-integrins in asthma

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.

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Silvestri¹,

Fregonese²,

Sabatini³

et al. 2001

“…ICAM-1, VCAM-1 and E-selectin are constitutively expressed on the epithelium of the bronchial mucosa both in normal subjects and patients with either atopic or nonatopic asthma [72], but their expression is more pronounced in asthmatics than control subjects [73,76,79,80]. In patients with allergic asthma, a further significant increase in ICAM-1 expression occurs after allergen challenge [81].…”

Section: Icam-1 In Allergic Inflammation and Asthmamentioning

confidence: 99%

The role of ICAM-1 on T-cells in the pathogenesis of asthma

Stanciu¹,

Djukanović²

1998

The capacity of inflammatory cells to adhere is critical to inflammatory responses and involves an array of adhesion molecules grouped into distinct families. Intercellular adhesion molecule (ICAM)-1 has recently attracted much interest in view of increasing evidence that it plays a prominent role in allergic diseases such as asthma and rhinitis. Apart from its role in adhesion of inflammatory cells to vascular endothelium, the extracellular matrix and epithelium, ICAM-1 mediates T-cell/T-cell, T-cell/target cell and T-cell/B-cell interactions. ICAM-1 on the surface of T-cells is thought to participate in signal transduction and may thus modulate several functions including activation, proliferation, cytotoxicity and cytokine production. Because ICAM-1 is the receptor for the major group of rhinoviruses, the most important cause of acute asthma attacks, binding of rhinovirus (RV) to ICAM-1 on T-cells may, at least theoretically, modulate their function. We review here the role of ICAM-1 in asthma and focus more specifically on its expression on T-cells. We present evidence for a general increase in ICAM-1 expression in this disease including recent observations of enhanced expression on the surface of T-cells in the airways lumen. Whilst the implications of intercellular adhesion molecule- upregulation in asthma remain to be fully elucidated, its participation in cell trafficking and activation are being considered as a target for treatment. We present here early attempts to interfere with intercellular adhesion molecule-1 as an adhesion molecule involved in cell influx and studies aimed preventing virus-induced exacerbations of asthma in children based on the knowledge that intercellular adhesion molecule-1 is the receptor for rhinoviruses.

“…Recent studies by CROMWELL et al [35] have demonstrated that human bronchial epithelial cells are capable of generating IL-8 and that the expression of this cytokine may be upregulated by TNF-α, a multifunctional cytokine shown to be active in increasing epithelial permeability in vitro [36], and increasing the expression of intercellular adhesion molecule-1 (ICAM-1) [37]. Indeed, studies of human bronchial epithelial cells have demonstrated that these are also capable of expressing ICAM-1 [38], a member of the immunoglobulin supergene family, which is itself important due to its role in the recruitment and migration of neutrophils and eosinophils [39].…”

Section: (Fig 2)mentioning

confidence: 99%

Bacterial-induced release of inflammatory mediators by bronchial epithelial cells

Khair¹,

Davies²,

Devalia³

1996

165

118