title: Corticosteroids inhibit rhinovirus-induced intercellular adhesion molecule-1 up-regulation and promoter activation on respiratory epithelial cells.
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-kappaB-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: University Medicine, University of Southampton, Southampton General Hospital, Southampton, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Papi
authors.forename: N G
authors.initials: NG
authors.lastname: Papadopoulos
authors.forename: K
authors.initials: K
authors.lastname: Degitz
authors.forename: S T
authors.initials: ST
authors.lastname: Holgate
authors.forename: S L
authors.initials: SL
authors.lastname: Johnston
mesh_terms: D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D002461:Cell Line, Transformed; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000821:virology; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000276:immunology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D012229:Rhinovirus / Q000187:drug effects / Q000276:immunology* / Q000472:pathogenicity; D015533:Transcriptional Activation / Q000187:drug effects / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects* / Q000276:immunology; D014779:Virus Replication / Q000187:drug effects / Q000276:immunology
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D018799:Intercellular Adhesion Molecule-1