Erythromycin suppresses nuclear factor-kappaB and activator protein-1 activation in human bronchial epithelial cells.
Erythromycin (EM), and related 14-member macrolide antibiotics, has attracted attention for its effectiveness in airway diseases including diffuse panbronchiolitis and sinobronchial syndrome. However, its molecular mechanisms remain unknown. We evaluated the effects of EM on activation of several transcription factors, including nuclear factor-kappaB (NF-kappaB) and activator protein-1 (AP-1) in human bronchial epithelial cell line BET-1A, which are known to regulate the expression of many proinflammatory cytokines and chemokines such as interleukin-8 (IL-8). BET-1A cells were cultured with hormonally defined Ham's F12 medium, and were stimulated by phorbol myristate acetate (PMA). EM suppressed mRNA expression as well as the release of IL-8 at therapeutic and noncytotoxic concentrations (% inhibition of IL-8 protein release: 42.2 +/- 5.5%, at 10(-6) M). Furthermore, electrophoretic mobility shift assays revealed that EM inhibited the activations of NF-kappaB and AP-1 induced by PMA in BET-1A cells. These data indicate that EM has inhibitory effects not only on the mRNA expression and release of IL-8, but also on the activation of transcription factors NF-kappaB and AP-1. Our findings support the concept that the recruitment of neutrophils in airway diseases may be regulated by NF-kappaB and AP-1.
Desaki
M
M
Department of Respiratory Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan. DESAKI-PHY@h.u-tokyo.ac.jp
Takizawa
H
H
Ohtoshi
T
T
Kasama
T
T
Kobayashi
K
K
Sunazuka
T
T
Omura
S
S
Yamamoto
K
K
Ito
K
K
D001980:Bronchi; D002460:Cell Line; D004917:Erythromycin / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics*; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D020545:Respiratory Mucosa / Q000187:drug effects / Q000502:physiology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects
D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D004917:Erythromycin; D013755:Tetradecanoylphorbol Acetate