Effect of ciprofloxacin on the activation of the transcription factors nuclear factor κB, activator protein-1 and nuclear factor-interleukin-6, and interleukin-6 and interleukin-8 mRNA expression in a human endothelial cell line

2000 ◽  
Vol 99 (5) ◽  
pp. 405 ◽  
Author(s):  
Helen F. GALLEY ◽  
Jatinder K. DHILLON ◽  
Ross L. PATERSON ◽  
Nigel R. WEBSTER
2000 ◽  
Vol 99 (5) ◽  
pp. 405-410 ◽  
Author(s):  
Helen F. GALLEY ◽  
Jatinder K. DHILLON ◽  
Ross L. PATERSON ◽  
Nigel R. WEBSTER

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 α- and IL-1β-mediated activation of the transcription factors nuclear factor κB (NFκB), 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 NFκB or AP-1. However, NF-IL-6 binding was decreased in the presence of 100 µg/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 NFkB 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.


2000 ◽  
Vol 59 (8) ◽  
pp. 997-1005 ◽  
Author(s):  
Alvaro Puga ◽  
Sonya J Barnes ◽  
Ching-yi Chang ◽  
Huan Zhu ◽  
Kenneth P Nephew ◽  
...  

2005 ◽  
Vol 90 (1) ◽  
pp. 237-246 ◽  
Author(s):  
Vasso Terzidou ◽  
Suren R. Sooranna ◽  
Louise U. Kim ◽  
Steve Thornton ◽  
Phillip R. Bennett ◽  
...  

Abstract Oxytocin receptor (OTR) expression is increased before the onset of labor in all models of parturition. However, the mechanisms responsible for the increase in OTR expression are uncertain. Animal data suggest that uterine stretch increases OTR mRNA expression. In primary cultures of human uterine smooth muscle cells obtained from nonpregnant (NP) women and pregnant women before (NL) and after (L) the onset of labor, we investigated the effect of stretch on the expression of OTR mRNA and DNA binding of activator protein-1 (AP-1), CCAAT/enhancer binding protein (C/EBP)β, and nuclear factor-κB transcription factors. OTR expression was least in NL, intermediate in NP, and greatest in L cells. Stretch of NL cells resulted in up-regulation of OTR mRNA expression associated with increased OTR gene promoter activity. Stretch of NP and L cells did not affect OTR mRNA expression. The increased promoter activity was associated with increased DNA binding of C/EBP and AP-1 but not nuclear factor-κB transcription factors. Overexpression of C/EBP, but not AP-1, increased OTR promoter activity. We conclude that stretch of NL cells results in increased OTR mRNA expression probably through increased C/EBPβ DNA binding. These data suggest that stretch contributes to the massive increase in OTR expression before the onset of human labor.


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