Effect of ciprofloxacin on the activation of the transcription factors nuclear factor kappaB, activator protein-1 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-1beta-mediated activation of the transcription factors nuclear factor kappaB (NFkappaB), activator protein-1 (AP-1) and nuclear factor IL-6 (NF-IL-6) using an electrophoretic mobility shift 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 NFkappaB or AP-1. However, NF-IL-6 binding was decreased in the presence of 100 microg/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 NFkappaB 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.
Galley
H F
HF
Academic Unit of Anaesthesia & Intensive Care, University of Aberdeen, Institute of Medical Sciences, Foresterhill, Aberdeen, AB 25 2ZD, Scotland. h.f.galley@abdn.ac.uk
Dhillon
J K
JK
Paterson
R L
RL
Webster
N R
NR
D000890:Anti-Infective Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002939:Ciprofloxacin / Q000494:pharmacology*; D004586:Electrophoresis; D004727:Endothelium / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics; D016209:Interleukin-8 / Q000235:genetics; D016328:NF-kappa B / Q000187:drug effects; D020871:RNA Stability; D012333:RNA, Messenger / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects*; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects
D000890:Anti-Infective Agents; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D014409:Tumor Necrosis Factor-alpha; D002939:Ciprofloxacin