Erythromycin inhibits rhinovirus infection in cultured human tracheal epithelial cells.
To examine the effects of erythromycin on rhinovirus (RV) infection in airway epithelium, primary cultures of human tracheal epithelial cells were infected with the RV major subgroup, RV14, and the minor subgroup, RV2. Infection was confirmed by increases in viral RNA of the infected cells and viral titers of the supernatants. RV14 upregulated the expression of the mRNA and protein of intercellular adhesion molecule-1 (ICAM-1), the major RV receptor, and it increased the cytokine production. Erythromycin reduced the supernatant RV14 titers, RV14 RNA, the susceptibility to RV14 infection, and the production of ICAM-1 and cytokines. Erythromycin also reduced the supernatant RV2 titers, RV2 RNA, the susceptibility to RV2 infection, and cytokine production, although the inhibitory effects of erythromycin on the expression of the low-density lipoprotein receptor, the minor RV receptor, were small. Erythromycin reduced the nuclear factor-kappaB activation by RV14 and decreased the number of acidic endosomes in the epithelial cells. These results suggest that erythromycin inhibits infection by the major RV subgroup by reducing ICAM-1 and infection by both RV subgroups by blocking the RV RNA entry into the endosomes. Erythromycin may also modulate airway inflammation by reducing the production of proinflammatory cytokines and ICAM-1 induced by RV infection.
Suzuki
Tomoko
T
Department of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, Sendai, Japan.
Yamaya
Mutsuo
M
Sekizawa
Kiyohisa
K
Hosoda
Masayoshi
M
Yamada
Norihiro
N
Ishizuka
Satoshi
S
Yoshino
Akiko
A
Yasuda
Hiroyasu
H
Takahashi
Hidenori
H
Nishimura
Hidekazu
H
Sasaki
Hidetada
H
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D003139:Common Cold / Q000188:drug therapy / Q000378:metabolism / Q000821:virology*; D016207:Cytokines / Q000378:metabolism; D004917:Erythromycin / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000032:analysis; D011973:Receptors, LDL / Q000378:metabolism; D020545:Respiratory Mucosa / Q000378:metabolism / Q000821:virology*; D012229:Rhinovirus / Q000187:drug effects* / Q000254:growth & development; D014132:Trachea / Q000378:metabolism / Q000821:virology*
D000900:Anti-Bacterial Agents; D016207:Cytokines; D016328:NF-kappa B; D012367:RNA, Viral; D011973:Receptors, LDL; D018799:Intercellular Adhesion Molecule-1; D004917:Erythromycin