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 (pNFκB 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