title: Effects of a novel nonantibiotic macrolide, EM900, on cytokine and mucin gene expression in a human airway epithelial cell line.
abstract: OBJECTIVE
  Long-term macrolide therapy is an effective treatment for chronic sinusitis and diffuse panbronchiolitis. However, long-term use of macrolides may promote the growth of drug-resistant bacteria; therefore, development of macrolides with no antibacterial action is desirable. A new erythromycin (EM) derivative, (8R,9S)- 8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A (EM900), does not possess antibacterial action.
  
  
  METHODS
  To determine whether EM900 induced a clinically relevant anti-inflammatory response and repressed mucin gene expression in cells derived from human airway epithelia, we assessed the effects of EM900 on IL-1β-induced inflammatory cytokines in A549 cells and MUC5AC gene expression in HM3-MUC5AC cells. We also investigated the effects of EM900 on IL-1β-induced NF-κB activation. We performed reporter gene assays and quantitative PCR in A549 and HM3-MUC5AC cells.
  
  
  RESULTS
  Both EM and EM900 suppressed IL-1β-induced IL-8 expression in A549 cells. EM900 also suppressed IL-1β-induced IL-1β and TNF-α expression in A549 cells. EM900 inhibited IL-1β-induced MUC5AC expression in HM3-MUC5AC cells. Both EM and EM900 suppressed IL-1β-induced NF-κB activation in A549 cells.
  
  
  CONCLUSIONS
  This study demonstrated that EM900 suppressed the induction of inflammatory cytokines and MUC5AC gene expression in cells derived from human airway epithelia, and our findings indicate that these effects may be mediated by the suppression of NF-κB activation.
authors: Department of Otorhinolaryngology, Head and Neck Surgery, Mie University Graduate School of Medicine, Tsu, Japan.
authors: Kazuya
authors: K
authors: Otsu
authors: Hajime
authors: H
authors: Ishinaga
authors: Shinya
authors: S
authors: Suzuki
authors: Akihiro
authors: A
authors: Sugawara
authors: Toshiaki
authors: T
authors: Sunazuka
authors: Satoshi
authors: S
authors: Omura
authors: Hirofumi
authors: H
authors: Jono
authors: Kazuhiko
authors: K
authors: Takeuchi
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D004917:Erythromycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000235:genetics / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics*; D018942:Macrolides / Q000494:pharmacology*; D055271:Mucin 5AC / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: C560918:(8R,9S)-8,9-dihydro-6,9-epoxy-8,9-anhydropseudoerythromycin A; D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D016209:Interleukin-8; C524678:MUC5AC protein, human; D018942:Macrolides; D055271:Mucin 5AC; D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D004917:Erythromycin