Vitamin D decreases cell death and inflammation in human umbilical vein endothelial cells and placental explants from pregnant women with preeclampsia cultured with TNF-alpha

This study evaluated the impact of vitamin D on Human Umbilical Vein Endothelial Cells (HUVEC) and inflammation in placental explants from women with preeclampsia (PE). HUVEC and explants from 10 late-onset PE (LOPE), 10 early-onset (EOPE), and 10 normotensive (NT) pregnant women were cultured with/without tumor necrosis factor (TNF-alpha) and VD. Interleukin-1 beta (IL-1 beta), 18 (IL-18), TNF-alpha, and TNF-related apoptosis-inducing ligand (TRAIL) were detected by ELISA. High mobility group box 1 (HMGB1) was determined by qPCR/Western blotting, and cell death by flow cytometry. Statistical significance was accepted at p < .05. Compared to the NT group, the endogenous levels of IL-1 beta, TNF-alpha, and IL-18 were higher in the PE group. The stimulus with TNF-alpha increased cytokines in NT, TNF-alpha in EOPE/LOPE, IL-18 in LOPE, and all cytokines in HUVEC. TNF-alpha+VD treatment decreased cytokines in explant and HUVEC supernatants. TRAIL was higher in EOPE versus NT, while TNF-alpha increased this receptor in NT versus control. In HUVEC, TNF-alpha increased TRAIL versus control, and TNF-alpha+VD decreased levels compared to only TNF-alpha stimulus. Protein expression of HMGB1 was higher in explant cultures treated with TNF-alpha and decreased after TNF-alpha+VD treatment in all groups, and gene/protein expression in HUVEC. Gene expression was elevated in EOPE versus NT and LOPE, and TNF-alpha increased HMGB1 in NT versus control, while TNF-alpha+VD decreased mRNA levels in EOPE. TNF-alpha stimulus increased late apoptosis in HUVEC, while VD increased viability. These in vitro observations suggest that VD administration to women with preeclampsia may be beneficial in reducing placental inflammation and cell death.