title: Inhibitory effects of tiotropium on rhinovirus infection in human airway epithelial cells.
abstract: Infection by rhinoviruses (RVs) causes exacerbations of chronic obstructive pulmonary disease (COPD). The long-acting anti-cholinergic agent tiotropium reduces the frequency of COPD exacerbations, but the inhibitory effects of tiotropium on the COPD exacerbations induced by RVs are unclear. Likewise, the effects of tiotropium on RVs infection remain to be studied. To examine the effects of tiotropium on RV infection and RV infection-induced airway inflammation, human tracheal epithelial cells were infected with a major group RV, type 14 RV (RV14). RV14 infection increased the viral titre and the amount of pro-inflammatory cytokines, including interleukin (IL)-1β and -6, in supernatant fluids and the amount of RV14 RNA in cells. Tiotropium reduced RV14 titres, RNA and cytokine concentrations, and susceptibility to RV14 infection. Tiotropium reduced the expression of intercellular adhesion molecule (ICAM)-1, the receptor for RV14, and the number of cellular acidic endosomes, which allow RV14 RNA to enter the cytoplasm. Tiotropium inhibited the activation of nuclear factor-(κ)B proteins, including p50 and p65, in the nuclear extracts, and it increased the cytosolic amount of inhibitory κB-α. Tiotropium may inhibit RV14 infection by reducing the levels of ICAM-1 and acidic endosomes and may also modulate airway inflammation in rhinovirus infection.
authors.affiliation: Dept of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan. myamaya@med.tohoku.ac.jp
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishimura
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Hatachi
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yasuda
authors.forename: Xue
authors.initials: X
authors.lastname: Deng
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagatomi
mesh_terms: D001993:Bronchodilator Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D010850:Picornaviridae Infections / Q000188:drug therapy*; D020545:Respiratory Mucosa / Q000378:metabolism*; D012229:Rhinovirus / Q000187:drug effects; D012602:Scopolamine Derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D000069447:Tiotropium Bromide; D014132:Trachea / Q000166:cytology
chemical_list: D001993:Bronchodilator Agents; D016207:Cytokines; D012602:Scopolamine Derivatives; D018799:Intercellular Adhesion Molecule-1; D000069447:Tiotropium Bromide