Vitamin D attenuates lipopolysaccharide-induced inflammatory response in endothelial cells through inhibition of PI3K/Akt/NF-kappa B signaling pathway

摘要

Inflammation and endothelial cells contribute to the pathogenesis of various cardiovascular diseases (CVDs). Vitamin D is associated with a decreased risk of inflammation related diseases including CVDs. However, the links between vitamin D, endothelial cells and vascular inflammation remain to be elucidated. In this study, we investigated the anti-inflammatory effect of vitamin D in lipopolysaccharide (LPS)-activated endothelial cells and the related signaling pathways. 1,25(OH)(2)D-3 treatment significantly suppressed LPS-induced upregulation of COX-2, TNF-alpha, IL-6 and PGE2 in Human umbilical vein endothelial cells (HUVECs). 1,25(OH)(2)D-3 inhibited LPS-stimulated phosphorylation of Akt at S473 and T308, I kappa B alpha phosphorylation, and nuclear accumulation of NF-kappa B. Blocking PI3K signaling abolished the inhibitory effect of 1,25(OH)(2)D-3 on LPS-induced increase of Akt S473 phosphorylation and COX-2 expression. Blocking NF-kappa B signaling blunted the suppression effect of 1,25(OH) 2 D 3 on I kappa B alpha phosphorylation, NF-kappa B accumulation in the nucleus and COX-2 expression. These results indicate that 1,25(OH)(2)D-3 suppresses inflammatory response in LPS-induced HUVECs through PI3K/Akt/NF-kappa B signaling pathway.