title: Effect of desloratadine and loratadine on rhinovirus-induced intercellular adhesion molecule 1 upregulation and promoter activation in respiratory epithelial cells.
abstract: BACKGROUND
  Rhinoviruses have been recently associated with the majority of asthma exacerbations for which current therapy is inadequate. Intercellular adhesion molecule 1 (ICAM-1) has a central role in airway inflammation in asthma, and it is the receptor for 90% of rhinoviruses. Rhinovirus infection of airway epithelium induces ICAM-1. Desloratadine and loratadine are compounds belonging to the new class of H(1)-receptor blockers. Anti-inflammatory properties of antihistamines have been recently documented, although the underlying molecular mechanisms are not completely defined.
  
  
  OBJECTIVE
  We have investigated the effects of desloratadine and loratadine on rhinovirus-induced ICAM-1 expression, mRNA upregulation, and promoter activation.
  
  
  METHODS
  Cultured primary bronchial or transformed (A549) respiratory epithelial cells were pretreated with desloratadine and loratadine for 16 hours and infected with rhinovirus type 16 for 8 hours. ICAM-1 surface expression was evaluated with flow cytometry, and ICAM-1 mRNA was evaluated with specific RT-PCR. In A549 cells promoter activation was evaluated with a chloramphenicol acetyltransferase assay, and binding activity of nuclear factor kappa B in nuclear extracts was evaluated with an electrophoretic mobility shift assay.
  
  
  RESULTS
  Desloratadine and loratadine (0.1-10 micromol/L) inhibited rhinovirus-induced ICAM-1 upregulation in both primary bronchial or transformed (A549) respiratory epithelial cells. In A549 cells the 2 compounds showed a dose-dependent inhibition with similar efficacy (inhibitory concentration of 50%, 1 micromol/L). Desloratadine and loratadine also inhibited ICAM-1 mRNA induction caused by rhinovirus infection in a dose-dependent manner, and they completely inhibited rhinovirus-induced ICAM-1 promoter activation. Desloratadine also inhibited rhinovirus-induced nuclear factor kappa B activation. Desloratadine and loratadine had no direct effect on rhinovirus infectivity and replication in cultured epithelial cells.
  
  
  CONCLUSIONS
  These effects are unlikely to be mediated by H(1)-receptor antagonism and suggest a novel mechanism of action that may be important for the therapeutic control of virus-induced asthma exacerbations.
authors.affiliation: University Medicine, University of Southampton, Southampton, UK.
authors.forename: A
authors.initials: A
authors.lastname: Papi
authors.forename: N G
authors.initials: NG
authors.lastname: Papadopoulos
authors.forename: L A
authors.initials: LA
authors.lastname: Stanciu
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: D001249:Asthma / Q000209:etiology; D001980:Bronchi / Q000166:cytology / Q000187:drug effects / Q000821:virology; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006367:HeLa Cells; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D017336:Loratadine / Q000031:analogs & derivatives / Q000494:pharmacology*; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects* / Q000821:virology*; D012229:Rhinovirus / Q000254:growth & development*; D015533:Transcriptional Activation; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D006634:Histamine H1 Antagonists; D016328:NF-kappa B; D018799:Intercellular Adhesion Molecule-1; D017336:Loratadine; C121345:desloratadine