title: Anti-infective control in human bronchiolar epithelial cells by mucin phenotypic changes following uptake of N-acetyl-L-cysteine.
abstract: OBJECTIVE
  Aspiration pneumonia is infection of the respiratory tract resulting from accumulation of sputum in the larynx. N-acetyl-L-cysteine (NAC) might regulate mucin (MUC) expression and activate inherent anti-infective system in bronchiolar epithelial cells after cellular uptake, and therefore, serve as the preventative agent for chronic lung disease including aspiration pneumonia. The purpose of this in vitro study was to evaluate the effect of uptake of NAC by human bronchiolar epithelial cells on bacterial infection and regulations of mucin expression in association with cellular redox status under co-culture with a representative pathogen for hospital- and community-acquired pneumonia, Streptococcus pneumoniae.
  
  
  METHODS
  Human bronchiolar epithelial cells preincubated with or without 20 mM NAC for 3 h were co-cultured with or without bacteria for 8 h and evaluated with respect to cellular redox balance, expressions of various types of MUC, proinflammatory cytokines and mediators, and bacterial infection state by biochemical, genetic, and immunofluorescent assays.
  
  
  RESULTS
  Markedly increased intracellular reactive oxygen species and oxidized glutathione levels plus increased release and expression of proinflammatory cytokines and mediators were observed in cells co-cultured with bacteria. These bacteria-induced cellular redox disturbance and proinflammatory events were prevented and alleviated by pretreatment with NAC. Cells co-cultured with bacteria did not increase expression of anti-infective membranous MUC4 but exhibited increases in gel-forming MUC5AC expression and bacterial infection. However, NAC-pretreated cells avoided bacterial infection along with enhancement of MUC4, but not MUC5AC, expression.
  
  
  CONCLUSIONS
  Uptake of NAC by human bronchiolar epithelial cells prevented bacterial infection and upregulated membranous, but not gel-forming, MUC expression along with the increase in intracellular antioxidant level under co-culture conditions with S. pneumoniae.
authors: Chiaki
authors: C
authors: Koizumi
authors: a Department of Removable Prosthodontics and Gerodontology , Tokyo Dental College , Tokyo , Japan.
authors: Masahiro
authors: M
authors: Yamada
authors: a Department of Removable Prosthodontics and Gerodontology , Tokyo Dental College , Tokyo , Japan.
authors: Ken
authors: K
authors: Ishizaki
authors: a Department of Removable Prosthodontics and Gerodontology , Tokyo Dental College , Tokyo , Japan.
authors: Takayuki
authors: T
authors: Ueda
authors: a Department of Removable Prosthodontics and Gerodontology , Tokyo Dental College , Tokyo , Japan.
authors: Kaoru
authors: K
authors: Sakurai
mesh_terms: D000111:Acetylcysteine / Q000276:immunology / Q000378:metabolism*; D055745:Bronchioles / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000276:immunology / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D009077:Mucins / Q000096:biosynthesis* / Q000276:immunology; D010084:Oxidation-Reduction; D010641:Phenotype; D011015:Pneumonia, Aspiration / Q000276:immunology / Q000378:metabolism; D011018:Pneumonia, Pneumococcal / Q000276:immunology / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013296:Streptococcus pneumoniae
chemical_list: D009077:Mucins; D000111:Acetylcysteine
keywords: AP-1; Airway inflammation; Antimicrobial; Antioxidant; COX-2; Thiols