TY - JOUR
T1 - Macrolide antibiotics inhibit respiratory syncytial virus infection in human airway epithelial cells
AU - Asada, Masanori
AU - Yoshida, Motoki
AU - Suzuki, Tomoko
AU - Hatachi, Yukimasa
AU - Sasaki, Takahiko
AU - Yasuda, Hiroyasu
AU - Nakayama, Katsutoshi
AU - Nishimura, Hidekazu
AU - Nagatomi, Ryoichi
AU - Kubo, Hiroshi
AU - Yamaya, Mutsuo
N1 - Funding Information:
The authors thank Mr. Grant Crittenden for reading the manuscript. This study was partly supported by Abott-Japan Pharmaceutical Co., Ltd., Taisho-Toyama Pharmaceutical Co., Ltd. Japan, Health and Labour Sciences Research Grants for Research on Measures for Intractable Diseases from the Ministry of Health, Labour and Welfare (H20nannchiippann35) and the Respiratory Failure Research Group from the Ministry of Health, Labour and Welfare, Japan.
PY - 2009/8
Y1 - 2009/8
N2 - To examine the effects of macrolide antibiotics on RS virus infection in airways, human tracheal epithelial cells were pre-treated with bafilomycin A1 and clarithromycin, and infected with RS virus. Viral titers in supernatant fluids and RNA of RS virus, and concentrations of cytokines in supernatant fluids, including interleukin-6 increased with time after infection. Bafilomycin A1 and clarithromycin reduced viral titers in supernatant fluids of RS virus, RNA of RS virus, the susceptibility to RS virus infection, and concentrations of cytokines induced by virus infection. N-acetyl-S-geranylgeranyl-l-cysteine, an inhibitor for a small GTP binding protein of RhoA, isoform A of the Ras-homologus (Rho) family, an active form of which is associated with RS virus infection via binding to its fusion protein (F protein), reduced viral titers in supernatant fluids and RNA of RS virus. Bafilomycin A1 and clarithromycin inhibited RhoA activation induced by lysophosphatidic acid in the cells. Fasudil, an inhibitor of Rho kinase, also reduced viral titers in supernatant fluids and RNA of RS virus. These findings suggest that macrolide antibiotics may inhibit RS virus infection, partly through the reduced expression of F protein receptor, activated RhoA, and the inhibition of subsequent Rho kinase activation in human airway epithelial cells.
AB - To examine the effects of macrolide antibiotics on RS virus infection in airways, human tracheal epithelial cells were pre-treated with bafilomycin A1 and clarithromycin, and infected with RS virus. Viral titers in supernatant fluids and RNA of RS virus, and concentrations of cytokines in supernatant fluids, including interleukin-6 increased with time after infection. Bafilomycin A1 and clarithromycin reduced viral titers in supernatant fluids of RS virus, RNA of RS virus, the susceptibility to RS virus infection, and concentrations of cytokines induced by virus infection. N-acetyl-S-geranylgeranyl-l-cysteine, an inhibitor for a small GTP binding protein of RhoA, isoform A of the Ras-homologus (Rho) family, an active form of which is associated with RS virus infection via binding to its fusion protein (F protein), reduced viral titers in supernatant fluids and RNA of RS virus. Bafilomycin A1 and clarithromycin inhibited RhoA activation induced by lysophosphatidic acid in the cells. Fasudil, an inhibitor of Rho kinase, also reduced viral titers in supernatant fluids and RNA of RS virus. These findings suggest that macrolide antibiotics may inhibit RS virus infection, partly through the reduced expression of F protein receptor, activated RhoA, and the inhibition of subsequent Rho kinase activation in human airway epithelial cells.
KW - Bronchial asthma
KW - COPD
KW - Macrolide
KW - Respiratory syncytial virus
KW - RhoA
UR - http://www.scopus.com/inward/record.url?scp=67249092205&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=67249092205&partnerID=8YFLogxK
U2 - 10.1016/j.antiviral.2009.05.003
DO - 10.1016/j.antiviral.2009.05.003
M3 - Article
C2 - 19463856
AN - SCOPUS:67249092205
VL - 83
SP - 191
EP - 200
JO - Antiviral Research
JF - Antiviral Research
SN - 0166-3542
IS - 2
ER -