Effect of ciprofloxacin on the activation of the transcription factors nuclear factor kappa B, activator protein-I and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line

Quinolone antibiotics such as ciprofloxacin modify immune and inflammatory responses in some cells. We have shown previously that ciprofloxacin decreases the accumulation of interleukin (IL)-6 protein from a human endothelial cell line, whilst IL-8 protein production was increased. It is not known whether this occurs through effects on transcription and mRNA expression. We therefore investigated the effect of ciprofloxacin on mRNA for IL-6 and IL-8, and on three transcription factors known to be involved in the regulation of these cytokines. We investigated the effect of ciprofloxacin on tumour necrosis factor alpha- and IL-1 beta -mediated activation of the transcription factors nuclear factor kappaB (NF kappaB), activator protein-1 (AP-1) and nuclear factor IL-6 (NF-IL-6) using an electrophoretic mobility sh ift assay, and the effect on expression of mRNA for IL-6 and IL-8 by reverse transcriptase-PCR in the EAhy926 endothelial cell line. Ciprofloxacin decreased IL-6 mRNA (P < 0.05) and increased IL-8 mRNA (P < 0.05) expression. Ciprofloxacin did not modulate activation of NF kappaB or AP-1. However, NF-IL-6 binding was decreased in the presence of 100 mug/ml ciprofloxacin (P < 0.05). The study shows that ciprofloxacin-mediated decreased IL-6 release by a human endothelial cell line is reflected by decreased mRNA expression and decreased NF-IL-6 but not NF<kappa>B or AP-1 activation. Increased IL-8 mRNA in response to ciprofloxacin was not reflected by altered transcription factor activation and may represent increased mRNA stability.