NF-kappaB and AP-1 are required for cyclo-oxygenase 2 gene expression in amnion epithelial cell line (WISH).
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.
Allport
V C
VC
Imperial College School of Medicine, Institute of Obstetrics and Gynaecology, Queen Charlotte's and Chelsea Hospital, London, UK.
Slater
D M
DM
Newton
R
R
Bennett
P R
PR
D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D001665:Binding Sites; D015153:Blotting, Western; D002460:Cell Line / Q000187:drug effects; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D007527:Isoenzymes / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins; D016297:Mutagenesis, Site-Directed; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism*
D007375:Interleukin-1; D007527:Isoenzymes; D008565:Membrane Proteins; D016328:NF-kappa B; D011994:Recombinant Proteins; D018808:Transcription Factor AP-1; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone