Corticosteroids inhibit rhinovirus-induced intercellular adhesion molecule-1 up-regulation and promoter activation on respiratory epithelial cells

Background: Rhinoviruses are associated with the majority of asthma exacerb ations. To date, the pathogenesis of virus-induced asthma exacerbations is still unclear, and no safe effective therapy is available, Intercellular ad hesion molecule-1 (ICAM-1) has a central role in inflammatory cell recruitm ent to the airways in asthma and is the receptor for 90% of rhinoviruses. W e have previously shown that rhinovirus infection of lower airway epitheliu m induces ICAM-1 expression by a transcriptional mechanism that is critical ly nuclear factor-kappa B-dependent. Objective: The purpose of this study was to investigate the effect of syste mic (hydrocortisone [HC], dexamethasone [DM]) and topical (mometasone furoa te [MF]) corticosteroids on rhinovirus-induced ICAM-1 up-regulation. Methods: Cultured primary bronchial or transformed (A549) respiratory epith elial cells were pretreated with corticosteroids for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluate d by flow cytometry, In A549 cells ICAM-1 messenger RNA was evaluated by sp ecific 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 A 549 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 res pectively). MF also inhibited ICAM-1 messenger RNA induction by rhinovirus infection in a dose-dependent manner. MF completely inhibited rhinovirus-in duced ICAM-1 promoter activation. HC, DM, and MF had no direct effect on rh inovirus infectivity and replication in cultured cells. Conclusion: Corticosteroids decrease rhinovirus-induced ICAM-1 up-regulatio n in respiratory epithelial cells and modulate pretranscriptional mechanism s. This effect may be important for the therapeutic control of virus-induce d asthma exacerbations.