Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells.
Type A human seasonal influenza (FluA) virus infection causes exacerbations of bronchial asthma and chronic obstructive pulmonary disease (COPD). l-carbocisteine, a mucolytic agent, reduces the frequency of common colds and exacerbations in COPD. However, the inhibitory effects of l-carbocisteine on FluA virus infection are uncertain. We studied the effects of l-carbocisteine on FluA virus infection in airway epithelial cells. Human tracheal epithelial cells were pretreated with l-carbocisteine and infected with FluA virus (H(3)N(2)). Viral titers in supernatant fluids, RNA of FluA virus in the cells, and concentrations of proinflammatory cytokines in supernatant fluids, including IL-6, increased with time after infection. l-carbocisteine reduced viral titers in supernatant fluids, RNA of FluA virus in the cells, the susceptibility to FluA virus infection, and concentrations of cytokines induced by virus infection. The epithelial cells expressed sialic acid with an alpha2,6-linkage (SAalpha2,6Gal), a receptor for human influenza virus on the cells, and l-carbocisteine reduced the expression of SAalpha2,6Gal. l-carbocisteine reduced the number of acidic endosomes from which FluA viral RNA enters into the cytoplasm and reduced the fluorescence intensity from acidic endosomes. Furthermore, l-carbocisteine reduced NF-kappaB proteins including p50 and p65 in the nuclear extracts of the cells. These findings suggest that l-carbocisteine may inhibit FluA virus infection, partly through the reduced expression of the receptor for human influenza virus in the human airway epithelial cells via the inhibition of NF-kappaB and through increasing pH in endosomes. l-carbocisteine may reduce airway inflammation in influenza virus infection.
Yamaya
Mutsuo
M
Dept. of Advanced Preventive Medicine for Infectious Disease, Tohoku Univ. School of Medicine, Seiryo-machi, Aoba-ku, Sendai, Japan. myamaya@m.tains.tohoku.ac.jp
Nishimura
Hidekazu
H
Shinya
Kyoko
K
Hatachi
Yukimasa
Y
Sasaki
Takahiko
T
Yasuda
Hiroyasu
H
Yoshida
Motoki
M
Asada
Masanori
M
Fujino
Naoya
N
Suzuki
Takaya
T
Deng
Xue
X
Kubo
Hiroshi
H
Nagatomi
Ryoichi
R
D000368:Aged; D000818:Animals; D002233:Carbocysteine / Q000627:therapeutic use*; D002478:Cells, Cultured; D004285:Dogs; D011992:Endosomes / Q000187:drug effects; D004847:Epithelial Cells / Q000821:virology; D005100:Expectorants / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects*; D007251:Influenza, Human / Q000188:drug therapy* / Q000517:prevention & control / Q000821:virology; D007378:Interleukins / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D016328:NF-kappa B / Q000096:biosynthesis; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000187:drug effects / Q000378:metabolism; D011991:Receptors, Virus / Q000096:biosynthesis; D014132:Trachea / Q000166:cytology
D005100:Expectorants; D007378:Interleukins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012367:RNA, Viral; D011991:Receptors, Virus; D002233:Carbocysteine