Abstract
To examine the effects of bafilomycin A(1), a blocker of vacuolar H(+)-ATPase, on rhinovirus (RV) infection in the airway epithelium, primary cultures of human tracheal epithelial cells were infected with RV14. Viral infection was confirmed by showing that viral RNA in the infected cells and the viral titers in the supernatants of infected cells increased with time. RV14 infection upregulated the production of cytokines and mRNA of intercellular adhesion molecule (ICAM)-1 in epithelial cells. Bafilomycin A(1) reduced the viral titers of RV14 and inhibited the production of cytokines and ICAM-1 before and after RV14 infection. Bafilomycin A(1) reduced susceptibility of epithelial cells to RV14 infection. RV14 increased activated nuclear factor-kappaB in the cells, and bafilomycin A(1) reduced the activated nuclear factor-kappaB. Bafilomycin A(1) decreased the number of acidic endosomes in the epithelial cells. These results suggest that bafilomycin A(1) may inhibit infection by RV14 by not only blocking RV RNA entry into the endosomes but also reducing ICAM-1 expression in the epithelial cells. Bafilomycin A(1) may therefore modulate airway inflammation after RV infection.
MeSH terms
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Amiloride / analogs & derivatives
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Amiloride / pharmacology
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Anti-Bacterial Agents / pharmacology*
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Benzyl Alcohols / pharmacology
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Cells, Cultured
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Cytokines / metabolism
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DNA / metabolism
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Dose-Response Relationship, Drug
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Endosomes / drug effects*
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Enzyme Inhibitors / pharmacology
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Female
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Guanidines / pharmacology
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Humans
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Hydrogen-Ion Concentration / drug effects
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism*
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Macrolides*
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Male
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Middle Aged
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NF-kappa B / metabolism
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Protein Binding / drug effects
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Proton-Translocating ATPases / antagonists & inhibitors
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Proton-Translocating ATPases / metabolism
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RNA, Messenger / metabolism
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Respiratory Mucosa / drug effects*
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Respiratory Mucosa / metabolism
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Respiratory Mucosa / pathology
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Respiratory Mucosa / virology
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Respiratory Tract Infections / drug therapy
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Respiratory Tract Infections / metabolism
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Respiratory Tract Infections / virology
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Rhinovirus / drug effects*
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Rhinovirus / growth & development
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Rhinovirus / metabolism
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Sodium-Hydrogen Exchangers / antagonists & inhibitors
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Trachea / cytology
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Vacuolar Proton-Translocating ATPases*
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Virus Replication / drug effects
Substances
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Anti-Bacterial Agents
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Benzyl Alcohols
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Cytokines
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Enzyme Inhibitors
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Guanidines
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Macrolides
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NF-kappa B
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RNA, Messenger
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Sodium-Hydrogen Exchangers
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Intercellular Adhesion Molecule-1
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Amiloride
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bafilomycin A1
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DNA
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Vacuolar Proton-Translocating ATPases
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Proton-Translocating ATPases
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FR 168888
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ethylisopropylamiloride