Corticosteroids inhibit rhinovirus-induced intercellular adhesion molecule-1 up-regulation and promoter activation on respiratory epithelial cells - 04/09/11
Abstract |
Background: Rhinoviruses are associated with the majority of asthma exacerbations. To date, the pathogenesis of virus-induced asthma exacerbations is still unclear, and no safe effective therapy is available. Intercellular adhesion molecule-1 (ICAM-1) has a central role in inflammatory cell recruitment to the airways in asthma and is the receptor for 90% of rhinoviruses. We have previously shown that rhinovirus infection of lower airway epithelium induces ICAM-1 expression by a transcriptional mechanism that is critically nuclear factor-κB-dependent. Objective: The purpose of this study was to investigate the effect of systemic (hydrocortisone [HC], dexamethasone [DM]) and topical (mometasone furoate [MF]) corticosteroids on rhinovirus-induced ICAM-1 up-regulation. Methods: Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with corticosteroids for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated by flow cytometry. In A549 cells ICAM-1 messenger RNA was evaluated by specific reverse transcription–PCR and promoter activation by chloramphenicol acetyltransferase assay. Results: We observed inhibition of rhinovirus-induced ICAM-1 up-regulation with corticosteroid pretreatment in both primary bronchial epithelial and A549 cells. In A549 cells systemic and topical corticosteroids demonstrated a dose-dependent inhibition with similar efficacy (inhibitory concentration 50% 10–10 mol/L, 10–11 mol/L, and 10–11 mol/L for HC, DM, and MF respectively). MF also inhibited ICAM-1 messenger RNA induction by rhinovirus infection in a dose-dependent manner. MF completely inhibited rhinovirus-induced ICAM-1 promoter activation. HC, DM, and MF had no direct effect on rhinovirus infectivity and replication in cultured cells. Conclusion: Corticosteroids decrease rhinovirus-induced ICAM-1 up-regulation in respiratory epithelial cells and modulate pretranscriptional mechanisms. This effect may be important for the therapeutic control of virus-induced asthma exacerbations. (J Allergy Clin Immunol 2000;105:318-26.)
Il testo completo di questo articolo è disponibile in PDF.Keywords : Asthma, rhinovirus, intercellular adhesion molecule-1, corticosteroids
Abbreviations : APRT:, ATCC:, CAT:, CO2:, CPE:, DM:, DMSO:, HC:, IC50:, ICAM-1:, MEM:, MF:, MOI:, mRNA:, NF-κB:, RT:, RV16:, TCID50:
Mappa
 | Supported by National Asthma Campaign grant No. 332, the University of Ferrara, Italy, the Deutsche Forschungsgemeinschaft grant No. 405/5 (K. D.), and Schering-Plough. |
| Reprint requests: Sebastian L. Johnston, MD, PhD, Department of Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine at St Mary’s, Norfolk Place, London W2 1PG, United Kingdom. |
 | 0091-6749/2000 $12.00 + 0 1/1/104107 |
Vol 105 - N° 2P1
P. 318-326 - Febbraio 2000 Ritorno al numero
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