Carbocisteine inhibits rhinovirus infection in human tracheal epithelial cells.
The aim of the study was to examine the effects of a mucolytic drug, carbocisteine, on rhinovirus (RV) infection in the airways. Human tracheal epithelial cells were infected with a major-group RV, RV14. RV14 infection increased virus titres and the cytokine content of supernatants. Carbocisteine reduced supernatant virus titres, the amount of RV14 RNA in cells, cell susceptibility to RV infection and supernatant cytokine concentrations, including interleukin (IL)-6 and IL-8, after RV14 infection. Carbocisteine reduced the expression of mRNA encoding intercellular adhesion molecule (ICAM)-1, the receptor for the major group of RVs. It also reduced the supernatant concentration of a soluble form of ICAM-1, the number and fluorescence intensity of acidic endosomes in the cells before RV infection, and nuclear factor-kappaB activation by RV14. Carbocisteine also reduced the supernatant virus titres of the minor group RV, RV2, although carbocisteine did not reduce the expression of mRNA encoding a low density lipoprotein receptor, the receptor for RV2. These results suggest that carbocisteine inhibits rhinovirus 2 infection by blocking rhinovirus RNA entry into the endosomes, and inhibits rhinovirus 14 infection by the same mechanism as well as by reducing intercellular adhesion molecule-1 levels. Carbocisteine may modulate airway inflammation by reducing the production of cytokines in rhinovirus infection.
Yasuda
H
H
Dept of Geriatric and Respiratory Medicine, Tohoku University School of Medicine, 1-Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan. yasuda@geriat.med.tohoku.ac.jp
Yamaya
M
M
Sasaki
T
T
Inoue
D
D
Nakayama
K
K
Yamada
M
M
Asada
M
M
Yoshida
M
M
Suzuki
T
T
Nishimura
H
H
Sasaki
H
H
D000368:Aged; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D002233:Carbocysteine / Q000494:pharmacology*; D011992:Endosomes / Q000378:metabolism; D004847:Epithelial Cells / Q000821:virology*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism; D010850:Picornaviridae Infections / Q000188:drug therapy*; D011973:Receptors, LDL / Q000378:metabolism; D012229:Rhinovirus / Q000378:metabolism*; D014132:Trachea / Q000821:virology*
D000891:Anti-Infective Agents, Local; D000998:Antiviral Agents; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011973:Receptors, LDL; D018799:Intercellular Adhesion Molecule-1; D002233:Carbocysteine