title: S-carboxymethylcysteine inhibits adherence of Streptococcus pneumoniae to human alveolar epithelial cells.
abstract: Streptococcus pneumoniae is a major pathogen of respiratory infections that utilizes platelet-activating factor receptor (PAFR) for firm adherence to host cells. The mucolytic agent S-carboxymethylcysteine (S-CMC) has been shown to exert inhibitory effects against infection by several respiratory pathogens including S. pneumoniae in vitro and in vivo. Moreover, clinical studies have implicated the benefits of S-CMC in preventing exacerbation of chronic obstructive pulmonary disease, which is considered to be related to respiratory infections. In this study, to assess whether the potency of S-CMC is attributable to inhibition of pneumococcal adherence to host cells, an alveolar epithelial cell line stimulated with interleukin-1α was used as a model of inflamed epithelial cells. Despite upregulation of PAFR by inflammatory activation, treatment with S-CMC efficiently inhibited pneumococcal adherence to host epithelial cells. In order to gain insight into the inhibitory mechanism, the effects of S-CMC on PAFR expression were also investigated. Following treatment with S-CMC, PAFR expression was reduced at both mRNA and post-transcriptional levels. Interestingly, S-CMC was also effective in inhibiting pneumococcal adherence to cells transfected with PAFR small interfering RNAs. These results indicate S-CMC as a probable inhibitor targeting numerous epithelial receptors that interact with S. pneumoniae.
authors: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors: Tomoko
authors: T
authors: Sumitomo
authors: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors: Masanobu
authors: M
authors: Nakata
authors: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka, Japan.
authors: Masaya
authors: M
authors: Yamaguchi
authors: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors: Yutaka
authors: Y
authors: Terao
authors: Department of Oral and Molecular Microbiology, Osaka University Graduate School of Dentistry, Osaka, Japan.
authors: Shigetada
authors: S
authors: Kawabata
mesh_terms: D056809:Alveolar Epithelial Cells / Q000382:microbiology*; D000891:Anti-Infective Agents, Local / Q000494:pharmacology*; D001422:Bacterial Adhesion / Q000187:drug effects*; D002233:Carbocysteine / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000382:microbiology; D006801:Humans; D010980:Platelet Membrane Glycoproteins / Q000187:drug effects / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000166:cytology / Q000382:microbiology; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000502:physiology
chemical_list: D000891:Anti-Infective Agents, Local; D010980:Platelet Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor; D002233:Carbocysteine