title: Azithromycin inhibits nontypeable Haemophilus influenzae-induced MUC5AC expression and secretion via inhibition of activator protein-1 in human airway epithelial cells.
abstract: Nontypeable Haemophilus influenzae (NTHi) is one of the most common pathogens in chronic airway infections and exacerbation. The hallmark of chronic respiratory diseases, including cystic fibrosis, diffuse panbronchiolitis and chronic obstructive pulmonary disease, is mucin overproduction. Prolonged macrolide antibiotic therapy at low doses is known to improve clinical outcome in patients with chronic respiratory diseases via anti-inflammatory effects. In this study, we investigated the effects of macrolide therapy on NTHi-induction of the MUC5AC mucin in human airway epithelial cells. A 15-membered macrolide, azithromycin, but not a 14-membered macrolide, clarithromycin, inhibited NTHi-induction of MUC5AC at both the mRNA and protein levels through selective suppression of activation of the transcription factor activator protein-1. Our findings suggest that each macrolide affects MUC5AC production in different ways and that azithromycin is more suitable for the treatment of NTHi-induced respiratory infection.
authors.affiliation: Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Araki
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yanagihara
authors.forename: Yoshitomo
authors.initials: Y
authors.lastname: Morinaga
authors.forename: Koichi
authors.initials: K
authors.lastname: Yamada
authors.forename: Shigeki
authors.initials: S
authors.lastname: Nakamura
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: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D017963:Azithromycin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D017291:Clarithromycin / Q000494:pharmacology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000382:microbiology; D006192:Haemophilus Infections / Q000188:drug therapy / Q000382:microbiology; D006193:Haemophilus influenzae / Q000378:metabolism*; D006801:Humans; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D017963:Azithromycin; D017291:Clarithromycin