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

H F Galley, J K Dhillon, R L Paterson, N R Webster

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)405-410
Number of pages6
JournalClinical Science
Volume99
Publication statusPublished - 2000

Keywords

  • activator protein-1
  • antibiotics
  • ciprofloxacin
  • interleukin-6
  • interleukin-8
  • nuclear factor kappa B
  • nuclear factor IL-6
  • STIMULATED HUMAN MONOCYTES
  • GENE-EXPRESSION
  • QUINOLONES
  • ACCUMULATION
  • PENETRATION
  • IL-1-BETA
  • PROMOTER
  • ALPHA
  • IL-6

Cite this

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title = "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",
abstract = "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 NFB 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.",
keywords = "activator protein-1, antibiotics, ciprofloxacin, interleukin-6, interleukin-8, nuclear factor kappa B, nuclear factor IL-6, STIMULATED HUMAN MONOCYTES, GENE-EXPRESSION, QUINOLONES, ACCUMULATION, PENETRATION, IL-1-BETA, PROMOTER, ALPHA, IL-6",
author = "Galley, {H F} and Dhillon, {J K} and Paterson, {R L} and Webster, {N R}",
year = "2000",
language = "English",
volume = "99",
pages = "405--410",
journal = "Clinical Science",
issn = "0143-5221",
publisher = "Portland Press Ltd.",

}

TY - JOUR

T1 - 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

AU - Galley, H F

AU - Dhillon, J K

AU - Paterson, R L

AU - Webster, N R

PY - 2000

Y1 - 2000

N2 - 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 NFB 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.

AB - 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 NFB 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.

KW - activator protein-1

KW - antibiotics

KW - ciprofloxacin

KW - interleukin-6

KW - interleukin-8

KW - nuclear factor kappa B

KW - nuclear factor IL-6

KW - STIMULATED HUMAN MONOCYTES

KW - GENE-EXPRESSION

KW - QUINOLONES

KW - ACCUMULATION

KW - PENETRATION

KW - IL-1-BETA

KW - PROMOTER

KW - ALPHA

KW - IL-6

M3 - Article

VL - 99

SP - 405

EP - 410

JO - Clinical Science

JF - Clinical Science

SN - 0143-5221

ER -