Magnesium sulfate suppresses inflammatory responses by human umbilical vein endothelial cells (HuVECs) through the NFκB pathway

Abstract

Dysfunctional endothelial cell activation and cytokines are implicated in preterm labor, a condition commonly treated with the tocolytic agent, magnesium sulfate (MgSO4). Based on recent findings showing the inflammatory effects of magnesium deficiency, we examined the effect of MgSO4 on human umbilical vein endothelial cell (HuVEC) inflammatory responses in vitro. HuVECs isolated from term umbilical cords were incubated with MgSO4 prior to stimulation with lipopolysaccharide (LPS) and then assessed for endothelial cell activation. Endothelial cell supernatants were assayed for inflammatory mediator production (interleukin-8; IL-8), and endothelial cell-associated intercellular adhesion molecule (ICAM-1) expression was determined. In the absence of LPS stimulation, MgSO4 had no effect on HuVEC responses. Treatment of HuVECs with MgSO4 prior to LPS stimulation inhibited inflammatory mediator production (p<0.05) and cell adhesion molecule expression (p<0.05) in a dose-dependent manner. Mechanistic studies showed that MgSO4 reduced NFκB nuclear translocation and protected cytoplasmic IκBα from degradation in LPS-treated HuVECs. In conclusion, MgSO4 inhibits endothelial cell activation, as measured by levels of IL-8 and ICAM-1 expression, via NFκB. Our results support the hypothesis that MgSO4 treatment may function as an anti-inflammatory agent during preterm labor.