Curcumin modulates endothelial permeability and monocyte transendothelial migration by affecting endothelial cell dynamics

Published on Nov 1, 2017in Free Radical Biology and Medicine6.17
· DOI :10.1016/J.FREERADBIOMED.2017.07.019
Laurent-Emmanuel Monfoulet8
Estimated H-index: 8
(INRA: Institut national de la recherche agronomique),
Sylvie Mercier7
Estimated H-index: 7
(INRA: Institut national de la recherche agronomique)
+ 4 AuthorsDragan Milenkovic32
Estimated H-index: 32
(INRA: Institut national de la recherche agronomique)
Abstract Curcumin is a phenolic compound that exhibits beneficial properties for cardiometabolic health. We previously showed that curcumin reduced the infiltration of immune cells into the vascular wall and prevented atherosclerosis development in mice. This study aimed to investigate the effect of curcumin on monocyte adhesion and transendothelial migration (TEM) and to decipher the underlying mechanisms of these actions. Human umbilical vein endothelial cells (HUVECs) were exposed to curcumin (0.5–1 μM) for 3 h prior to their activation by Tumor Necrosis Factor alpha (TNF-α). Endothelial permeability, monocyte adhesion and transendothelial migration assays were conducted under static condition and shear stress that mimics blood flow. We further investigated the impact of curcumin on signaling pathways and on the expression of genes using macroarrays. Pre-exposure of endothelial cells to curcumin reduced monocyte adhesion and their transendothelial migration in both static and shear stress conditions. Curcumin also prevented changes in both endothelial permeability and the area of HUVECs when induced by TNF-α. We showed that curcumin modulated the expression of 15 genes involved in the control of cytoskeleton and endothelial junction dynamic. Finally, we showed that curcumin inhibited NF-κB signaling likely through an antagonist interplay with several kinases as suggested by molecular docking analysis. Our findings demonstrate the ability of curcumin to reduce monocyte TEM through a multimodal regulation of the endothelial cell dynamics with a potential benefit on the vascular endothelial function barrier.
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