The Preeclamptic Environment Promotes the Activation of Transcription Factor Kappa B by P53/RSK1 Complex in a HTR8/SVneo Trophoblastic Cell Line

Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NF kappa B) in maternal and placental cells. Although the role of NF kappa B in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NF kappa B activation in a first trimester trophoblastic cell line (HTR8/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O-2) or normoxic (8% O-2) conditions. The results indicate that in HTR8/SVneo cells, the most widely studied NF kappa B pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O-2 in comparison to C 8% O-2. Therefore, other pathways may be responsible for NF kappa B activation. One such pathway depends on the activation of NF kappa B by the p53/RSK1 complex through its phosphorylation at Serine 536 (pNF kappa B Ser536). The data generated by our study show that inhibition of the p53/RSK1 pathway by p53-targeted siRNA results in a depletion of pNF kappa B Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O-2. Thus, the p53/RSK1 complex might play a critical role in the activation of NF kappa B in trophoblastic cells and preeclamptic placentas.