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.