NF-κB 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 β (IL-1β), 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-1β causes increased transcription of the COX-2 gene. Luciferase reporter constructs with site-directed mutagenesis of the two NF-κB 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-1β-treated WISH cells.