title: The non-antibiotic macrolide EM900 inhibits rhinovirus infection and cytokine production in human airway epithelial cells.
abstract: The anti-inflammatory effects of macrolides may be associated with a reduced frequency of exacerbation of chronic obstructive pulmonary disease (COPD). However, because the long-term use of antibiotics may promote the growth of drug-resistant bacteria, the development of a treatment to prevent COPD exacerbation with macrolides that do not exert anti-bacterial effects is necessary. Additionally, the inhibitory effects of nonantibiotic macrolides on the replication of rhinovirus (RV), which is the major cause of COPD exacerbation, have not been demonstrated. Primary cultures of human tracheal epithelial cells and nasal epithelial cells were pretreated with the nonantibiotic macrolide EM900 for 72 h prior to infection with a major group RV type 14 rhinovirus (RV14) and were further treated with EM900 after infection. Treatment with EM900 before and after infection reduced RV14 titers in the supernatants and viral RNA within the cells. Moreover, cytokine levels, including interleukin (IL)-1β and IL-6, were reduced in the supernatants following RV14 infection. Treatment with EM900 before and after infection also reduced the mRNA and protein expression of intercellular adhesion molecule-1 (ICAM-1), which is the receptor for RV14, after infection and reduced the activation of the nuclear factor kappa-B protein p50 in nuclear extracts after infection. Pretreatment with EM900 reduced the number and fluorescence intensity of the acidic endosomes through which RV RNA enters the cytoplasm. Thus, pretreatment with EM900 may inhibit RV infection by reducing the ICAM-1 levels and acidic endosomes and thus modulate the airway inflammation associated with RV infections.
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Nadine
authors.initials: N
authors.lastname: Lusamba Kalonji
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Laboratory of Rehabilitative Auditory Science, Tohoku University Graduate School of Biomedical Engineering, Sendai, Japan.
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Kawase
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Ota
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.affiliation: Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takeya
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Molecular Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Yanagisawa
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan Graduate School of Infection Control Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.affiliation: Department of Advanced Preventive Medicine for Infectious Disease, Tohoku University Graduate School of Medicine, Sendai, Japan myamaya@med.tohoku.ac.jp.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
keywords: Airway epithelial cell; COPD; EM900; inflammation; rhinovirus