UL16-Binding Protein 1 Induced HTR-8/SVneo Autophagy via NF-κB Suppression Mediated by TNF-α Secreted through uNK Cells

Abstract

UL16-binding protein 1(ULBP1) has been reported to inhibit trophoblast invasion through the modification of secretion functions of uNK cells in the previous study, but its mechanisms remain unclear. In this study, we investigated the related mechanism by which upregulated ULBP1 expression impaired trophoblast invasion. We found that conditioned media with ULBP1 increased autophagy in HTR-8/SVneo, and anti-TNF-α-neutralizing antibody rescued the autophagy caused by the conditioned medium. We further found TNF-α induced autophagy in trophoblast cells in a dose-dependent way and accompanied by a decreased activity of nuclear factor-kappa B (NF-κB). Inhibition of NF-κB activation by chemical inhibitor augmented these autophagic responses to TNF-α in the cells. In addition, interruption NF-κB caused a significant decrease in HTR-8/SVneo invasion and enhanced the inhibition effect of TNF-α on HTR-8/SVneo invasion. Taken together, these findings suggest that TNF-α is able to regulate autophagic activity via suppressing NF-κB, which might be the mechanism related to ULBP1 in preeclampsia pathogenesis.