Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells

Mutsuo Yamaya, Hidekazu Nishimura, Kyoko Shinya, Yukimasa Hatachi, Takahiko Sasaki, Hiroyasu Yasuda, Motoki Yoshida, Masanori Asada, Naoya Fujino, Takaya Suzuki, Xue Deng, Hiroshi Kubo, Ryoichi Nagatomi

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

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 3N2). 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 α2,6-linkage (SAα2,6Gal), a receptor for human influenza virus on the cells, and L-carbocisteine reduced the expression of SAα2,6Gal. 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-κB 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-κB and through increasing pH in endosomes. L-carbocisteine may reduce airway inflammation in influenza virus infection.

Original languageEnglish
Pages (from-to)L160-L168
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume299
Issue number2
DOIs
Publication statusPublished - 2010 Aug

Keywords

  • Bronchial asthma
  • Chronic obstructive pulmonary disease
  • SAα2,6Gal

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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