Abstract
Prostaglandins are known to play an important role in human labour and are used clinically to induce labour onset. Cytokines, e.g. interleukin 1 beta (IL-1beta), are up-regulated in the amniotic fluid late in gestation and can increase prostaglandin production through the expression of cyclo-oxygenase 2 (COX-2), the prostaglandin synthetic isoform involved in human labour. We demonstrate in immortalized amnion epithelial (WISH) cells, that IL-1beta causes increased transcription of the COX-2 gene. Luciferase reporter constructs with site-directed mutagenesis of the two NF-kappaB sites and an AP-1 site in the COX-2 promoter showed reduced expression of luciferase in transient transfection studies. This suggests that the binding of transcription factors to these sites is essential for the regulation of COX-2 transcription in IL-1beta-treated WISH cells.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amnion / cytology
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Amnion / drug effects
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Amnion / metabolism*
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Binding Sites
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Blotting, Western
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Cell Line / drug effects
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Cyclooxygenase 2
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Dinoprostone / metabolism
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Gene Expression Regulation
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Genes, Reporter
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Humans
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Interleukin-1 / metabolism
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Interleukin-1 / pharmacology
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Isoenzymes / drug effects
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Isoenzymes / genetics*
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Isoenzymes / metabolism
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Membrane Proteins
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Mutagenesis, Site-Directed
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Promoter Regions, Genetic
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Prostaglandin-Endoperoxide Synthases / drug effects
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Prostaglandin-Endoperoxide Synthases / genetics*
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Prostaglandin-Endoperoxide Synthases / metabolism
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Transcription Factor AP-1 / genetics
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Transcription Factor AP-1 / metabolism*
Substances
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Interleukin-1
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Isoenzymes
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Membrane Proteins
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NF-kappa B
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Recombinant Proteins
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Transcription Factor AP-1
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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Dinoprostone