title: Azithromycin, clarithromycin and telithromycin inhibit MUC5AC induction by Chlamydophila pneumoniae in airway epithelial cells.
abstract: BACKGROUND
  Airway mucus hypersecretion is an important problem in chronic respiratory diseases including bronchial asthma. Chlamydophila pneumoniae is recently confirmed to be a pathogen in bronchial asthma, but the relationship between C. pneumoniae and mucus hypersecretion is uncertain. In this study, we examined whether C. pneumoniae induces MUC5AC mucin in airway epithelial cells. We also examined the effects of macrolide and ketolide antibiotics on the C. pneumoniae-induced mucus production.
  
  
  METHODS
  MUC5AC production in bronchial epithelial cells after stimulation with C. pneumoniae was analyzed by ELISA and quantitative RT-PCR. NF-kappaB and phosphorylated ERK were also analyzed. For inhibition study, cells were pretreated with azithromycin, clarithromycin and telithromycin before stimulation.
  
  
  RESULTS
  C. pneumoniae dose-dependently induced MUC5AC production and gene expression. The ERK-NF-kappaB pathway was involved in C. pneumoniae-induced MUC5AC production. Macrolides and ketolides dose-dependently reduced C. pneumoniae-induced MUC5AC production. However, azithromycin was apparently less effective than the other antibiotics. Clarithromycin and telithromycin, but not azithromycin, reduced NF-kappaB activation.
  
  
  CONCLUSIONS
  Clarithromycin and telithromycin were thought to interfere with the signal pathways between ERK and NF-kappaB. These results suggest that airway mucus hypersecretion is one of the mechanisms of C. pneumoniae-induced bronchial asthma, and that macrolide and ketolide antibiotics represent a novel therapeutic intervention in these patients.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8501, Japan.
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Miyashita
authors.forename: Masafumi
authors.initials: M
authors.lastname: Seki
authors.forename: Koichi
authors.initials: K
authors.lastname: Izumikawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kakeya
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kohno
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D023521:Chlamydophila Infections / Q000378:metabolism*; D016993:Chlamydophila pneumoniae; D017291:Clarithromycin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis; D015870:Gene Expression / Q000187:drug effects; D048628:Ketolides / Q000494:pharmacology*; D051379:Mice; D055271:Mucin 5AC / Q000096:biosynthesis* / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D052002:NF-kappa B p50 Subunit / Q000096:biosynthesis / Q000235:genetics; D020545:Respiratory Mucosa / Q000166:cytology* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051996:Transcription Factor RelA / Q000096:biosynthesis / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D048628:Ketolides; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D017963:Azithromycin; D048049:Extracellular Signal-Regulated MAP Kinases; D017291:Clarithromycin; C106791:telithromycin