RRC ID 45162
Author Yamaya M, Nishimura H, Nadine L, Kubo H, Nagatomi R.
Title Formoterol and budesonide inhibit rhinovirus infection and cytokine production in primary cultures of human tracheal epithelial cells.
Journal Respir Investig
Abstract BACKGROUND:Long-acting β(2) agonists (LABAs) and inhaled corticosteroids (ICSs) reduce the frequency of exacerbations of chronic obstructive pulmonary disease and bronchial asthma. However, inhibitory effects of LABAs and ICSs on the replication of rhinovirus (RV), the major cause of exacerbations, have not been demonstrated.
METHODS:Primary cultures of human tracheal epithelial cells were infected with a major group RV, type 14 rhinovirus (RV14), to examine the effects of formoterol and budesonide on RV infection and infection-induced airway inflammation.
RESULTS:Treatment with formoterol and budesonide 72 h before and after RV14 infection reduced RV14 titers and cytokine concentrations, including interleukin (IL)-1β, IL-6 and IL-8, in supernatants and viral RNA within cells. Formoterol and budesonide reduced mRNA expression and protein concentration of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14. Formoterol reduced the number and fluorescence intensity of acidic endosomes through which RV RNA enters the cytoplasm. Formoterol and budesonide reduced the activation of the nuclear factor kappa-B protein p65 in nuclear extracts. The effects of formoterol plus budesonide were additive with respect to RV14 replication, cytokine production, ICAM-1 expression, acidic endosome fluorescence intensity, and p65 activation. The selective β(2)-adrenergic receptor antagonist, ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol], reversed the inhibitory effects of formoterol on RV14 titers and RNA levels, the susceptibility of cells to RV14 infection, cytokine production, acidic endosomes, ICAM-1 expression, and p65 activation.
CONCLUSIONS:Formoterol and budesonide may inhibit RV infection by reducing the ICAM-1 levels and/or acidic endosomes and modulate airway inflammation associated with RV infections.
Volume 52(4)
Pages 251-60
Published 2014-7
DOI 10.1016/j.resinv.2014.03.004
PII S2212-5345(14)00029-X
PMID 24998372
MeSH Adrenergic beta-2 Receptor Agonists / pharmacology* Aged Budesonide / pharmacology* Cells, Cultured Cytokines / metabolism* Epithelial Cells / metabolism* Epithelial Cells / virology* Ethanolamines / pharmacology* Female Formoterol Fumarate Glucocorticoids / pharmacology* Humans Intercellular Adhesion Molecule-1 / metabolism Male Picornaviridae Infections / virology* RNA, Viral / metabolism Rhinovirus / genetics Rhinovirus / pathogenicity Rhinovirus / physiology* Trachea / cytology* Transcription Factor RelA / metabolism Virus Replication / drug effects*
Human and Animal Cells