title: Inhibitory effects of carbocisteine on type A seasonal influenza virus infection in human airway epithelial cells.
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(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.
authors.affiliation: 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
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Yamaya
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Nishimura
authors.forename: Kyoko
authors.initials: K
authors.lastname: Shinya
authors.forename: Yukimasa
authors.initials: Y
authors.lastname: Hatachi
authors.forename: Takahiko
authors.initials: T
authors.lastname: Sasaki
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yasuda
authors.forename: Motoki
authors.initials: M
authors.lastname: Yoshida
authors.forename: Masanori
authors.initials: M
authors.lastname: Asada
authors.forename: Naoya
authors.initials: N
authors.lastname: Fujino
authors.forename: Takaya
authors.initials: T
authors.lastname: Suzuki
authors.forename: Xue
authors.initials: X
authors.lastname: Deng
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kubo
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Nagatomi
mesh_terms: 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
chemical_list: D005100:Expectorants; D007378:Interleukins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012367:RNA, Viral; D011991:Receptors, Virus; D002233:Carbocysteine