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.