Erythromycin suppresses nuclear factor-kappa B and activator protein-1 activation in human bronchial epithelial cells

Erythromycin (EM), and related 14-member macrolide antibiotics, has attract ed attention for its effectiveness in airway diseases including diffuse pan bronchiolitis and sinobronchial syndrome. However, its molecular mechanisms remain unknown, We evaluated the effects of EM on activation of several tr anscription factors, including nuclear factor-kappa B (NF-kappa B) and acti vator protein-1 (AP-1) in human bronchial epithelial cell line BET-1A, whic h are known to regulate the expression of many proinflammatory cytokines an d chemokines such as interleukin-8 (IL-8), BET-1A cells were cultured with hormonally defined Ham's F12 medium, and were stimulated by phorbol myrista te acetate (PMA). EM suppressed mRNA expression as well as the release of I L-8 at therapeutic and noncytotoxic concentrations (% inhibition of IL-8 pr otein release: 42.2 +/- 5.5%, at 10(-6) M), Furthermore, electrophoretic mo bility shift assays revealed that EM inhibited the activations of NF-kappa B 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-kappa B and AP-1. Our f indings support the concept that the recruitment of neutrophils in airway d iseases may be regulated by NF-kappa B and AP-1. (C) 1999 Academic Press.