title: Tulobuterol inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells.
abstract: A transdermal patch preparation of the β2 agonist tulobuterol has been designed to yield sustained β2 agonistic effects and has been used as a long-acting β2 agonist (LABA) in Japan. LABAs reduce the frequency of exacerbations of chronic obstructive pulmonary disease and bronchial asthma. However, inhibitory effects of LABAs on the replication of rhinovirus (RV), the major cause of exacerbations, have not been demonstrated. To examine the effects of tulobuterol on RV replication and on the production of the replication-induced pro-inflammatory cytokines, human tracheal epithelial cells were infected with a major group RV, type 14 rhinovirus (RV14). Tulobuterol reduced the RV14 titers and RNA levels; the concentrations of cytokines, including interleukin (IL)-1β, IL-6, and IL-8, in the supernatants; and susceptibility to RV14 infection. Tulobuterol reduced the expression of intercellular adhesion molecule-1 (ICAM-1), the receptor for RV14, and the number of acidic endosomes in the cells in which RV14 RNA enters the cytoplasm. Tulobuterol inhibited the activation of nuclear factor kappa B (NF-κB) proteins in nuclear extracts. A selective β2-adrenergic receptor antagonist, ICI 118551 [erythro-dl-1-(7-methylindan-4-yloxy)-3-isopropylaminobutan-2-ol], reversed the inhibitory effects of tulobuterol on the RV14 titers and RNA levels, the susceptibility to RV14 infection, cytokine production, and ICAM-1 expression. Tulobuterol may inhibit RV replication by reducing ICAM-1 expression and acidic endosomes and modulate airway inflammation during RV replication.
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine Sendai, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishimura
authors.forename: Lusamba
authors.initials: L
authors.lastname: Nadine
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Nagatomi
authors.initials: N
authors.lastname: Ryoichi
keywords: Acidic endosomes; human tracheal epithelial cells; rhinovirus; tulobuterol