RRC ID 43843
Author Yamaya M, Nishimura H, Hatachi Y, Yasuda H, Deng X, Sasaki T, Mizuta K, Kubo H, Nagatomi R.
Title Levofloxacin inhibits rhinovirus infection in primary cultures of human tracheal epithelial cells.
Journal Antimicrob Agents Chemother
Abstract Respiratory virus infections, including infections with rhinoviruses (RVs), are related to exacerbations of chronic obstructive pulmonary disease (COPD). A new quinolone antibiotic, levofloxacin (LVFX), has been used to treat bacterial infections that cause COPD exacerbations as well as bacterial infections that are secondary to viral infection in COPD patients. However, the inhibitory effects of LVFX on RV infection and RV infection-induced airway inflammation have not been studied. We examined the effects of LVFX on type 14 rhinovirus (RV14) (a major human RV) infection of human tracheal epithelial cells pretreated with LVFX. LVFX pretreatment reduced the RV14 titer, the level of cytokines in the supernatant, the amount of RV14 RNA in the cells after RV14 infection, and the cells' susceptibility to RV14 infection. LVFX pretreatment decreased the mRNA level of intercellular adhesion molecule 1 (ICAM-1), a receptor for RV14, in the cells and the concentration of the soluble form of ICAM-1 in the supernatant before RV14 infection. LVFX pretreatment also decreased the number and the fluorescence intensity of the acidic endosomes from which RV14 RNA enters the cytoplasm. LVFX pretreatment inhibited the activation of nuclear factor κB proteins, including p50 and p65, in nuclear extracts. LVFX pretreatment did not reduce the titers of RV2 (a minor human RV) but reduced the titers of RV15 (a major human RV). These results suggest that LVFX inhibits major-group rhinovirus infections in part by reducing ICAM-1 expression levels and the number of acidic endosomes. LVFX may also modulate airway inflammation in rhinoviral infections.
Volume 56(8)
Pages 4052-61
Published 2012-8-1
DOI 10.1128/AAC.00259-12
PII AAC.00259-12
PMID 22585227
PMC PMC3421613
MeSH Anti-Bacterial Agents / pharmacology Cells, Cultured Cytokines / metabolism Epithelial Cells / drug effects Epithelial Cells / virology Humans Intercellular Adhesion Molecule-1 / genetics Intercellular Adhesion Molecule-1 / metabolism* Levofloxacin* NF-kappa B / metabolism Ofloxacin / pharmacology* Picornaviridae Infections / drug therapy Picornaviridae Infections / virology RNA, Viral / biosynthesis Receptors, Virus / metabolism* Respiratory Mucosa / cytology Respiratory Mucosa / virology* Rhinovirus / drug effects* Rhinovirus / genetics Trachea / cytology Trachea / virology*
IF 4.904
Times Cited 12
WOS Category PHARMACOLOGY & PHARMACY MICROBIOLOGY
Resource
Human and Animal Cells