Azithromycin inhibits nontypeable Haemophilus influenzae-induced MUC5AC expression and secretion via inhibition of activator protein-1 in human airway epithelial cells.
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.
Araki
Nobuko
N
Department of Laboratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Yanagihara
Katsunori
K
Morinaga
Yoshitomo
Y
Yamada
Koichi
K
Nakamura
Shigeki
S
Yamada
Yasuaki
Y
Kohno
Shigeru
S
Kamihira
Shimeru
S
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
D000900:Anti-Bacterial Agents; C524678:MUC5AC protein, human; D055271:Mucin 5AC; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D017963:Azithromycin; D017291:Clarithromycin