title: Anti-inflammatory effects of a novel non-antibiotic macrolide, EM900, on mucus secretion of airway epithelium.
abstract: OBJECTIVE
  Low-dose, long-term use of 14-membered macrolides is effective for treatment of patients with chronic airway inflammation such as diffuse panbronchiolitis or chronic rhinosinusitis. However, long-term use of macrolides can promote the growth of drug-resistant bacteria, and the development of anti-inflammatory macrolides that lack antibiotic effects is desirable. Previously, we developed EM900, a novel 12-membered erythromycin A derivative, which has potent anti-inflammatory and immunomodulatory activities and lacks any antibacterial activity. We examined the anti-inflammatory effects of EM900 on mucus secretion from airway epithelial cells.
  
  
  METHODS
  To examine the in vivo effects of EM900 on airway inflammation, we induced hypertrophic and metaplastic changes of goblet cells in rat nasal epithelium via intranasal instillation of lipopolysaccharides. In vitro effects of EM900 on airway epithelial cells were examined using cultured human airway epithelial (NCI-H292) cells. Mucus secretion was evaluated via enzyme-linked immunosorbent assays with an anti-MUC5AC monoclonal antibody.
  
  
  RESULTS
  Oral administration of EM900 or clarithromycin (CAM) significantly inhibited LPS-induced mucus production from rat nasal epithelium. EM900, CAM, or erythromycin significantly inhibited MUC5AC secretion induced by tumor necrosis factor-α from NCI-H292 cells. MUC5AC mRNA expression was also significantly lower in EM900-treated cells.
  
  
  CONCLUSIONS
  These results indicated that a novel non-antibiotic macrolide, EM900 exerted direct inhibitory effects on mucus secretion from airway epithelial cells, and that it may have the potential to become a new anti-inflammatory drug for the treatment of chronic rhinosinusitis.
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan. Electronic address: itirotz@hotmail.com.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tojima
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Shino
authors.initials: S
authors.lastname: Shimizu
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Ogawa
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Kouzaki
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Omura
authors.affiliation: Kitasato Institute for Life Sciences, Kitasato University, Tokyo, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Sunazuka
authors.affiliation: Department of Otorhinolaryngology, Shiga University of Medical Science, Otsu, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Shimizu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D017291:Clarithromycin / Q000494:pharmacology; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D020397:Goblet Cells / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008070:Lipopolysaccharides / Q000494:pharmacology; D055271:Mucin 5AC / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D009093:Mucus / Q000187:drug effects* / Q000378:metabolism; D009297:Nasal Mucosa / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D020545:Respiratory Mucosa / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: C560918:(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A; D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D008070:Lipopolysaccharides; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin; D017291:Clarithromycin
keywords: EM900; Lipopolysaccharide; Macrolide; Mucus secretion; Nose