@article {598,
	title = {Effect of desloratadine and loratadine on rhinovirus-induced intercellular adhesion molecule 1 upregulation and promoter activation in respiratory epithelial cells},
	journal = {J Allergy Clin Immunol},
	volume = {108},
	number = {2},
	year = {2001},
	pages = {221-8},
	type = {Journal Article},
	abstract = {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.|We have investigated the effects of desloratadine and loratadine on rhinovirus-induced ICAM-1 expression, mRNA upregulation, and promoter activation.|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.|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.|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.},
	keywords = {Asthma Bronchi Epithelial Cells HeLa Cells Histamine H1 Antagonists Humans Intercellular Adhesion Molecule-1 Loratadine NF-kappa B Promoter Regions, Genetic Respiratory Mucosa Rhinovirus Transcriptional Activation Up-Regulation},
	issn = {0091-6749},
	doi = {10.1067/mai.2001.116861},
	url = {http://www.ncbi.nlm.nih.gov/pubmed/11496238},
	author = {Papi, A. and Papadopoulos, N. G. and Stanciu, L. A. and Degitz, K. and Holgate, S. T. and Johnston, S. L.}
}
