Lycopene inhibits TNF-α-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion

Inflammatory mediators such as TNF-α and interleukin (IL)-1β, and IL-8, which can enhance binding of low-density lipoprotein (LDL) to endothelium and upregulate expression of leukocyte adhesion molecules on endothelium during atherogenesis. Lycopene, a natural carotenoid from tomato and other sources, has been shown to prevent cardiovascular diseases in epidemiological studies. However, its anti-inflammatory action mechanism remains unclear. In the present study, we studied the effect of lycopene on TNF-α-induced signaling in human umbilical endothelial cells (HUVECs). We found that TNF-α-induced intercellular adhesion molecule-1 (ICAM-1) expression in HUVECs was inhibited by lycopene, whereas cyclooxygenase-2 (COX-2) and platelet-endothelial cell adhesion molecule (PECAM-1) expression were not affected. A further analysis indicated that lycopene attenuated TNF-α-induced IκB phosphorylation, NF-κB expression, and NF-κB p65 translocation from cytosol to nucleus. In line with this, TNF-α-induced NF-κB-DNA but not AP1-DNA complexes formation was inhibited by lycopene, as determined by the electrophoretic mobility shift assay (EMSA). On the other hand, lycopene did not affect TNF-α-induced p38 and extracellular matrix-regulated kinase1/2 (ERK1/2) phosphorylation and interferon-γ (IFN-γ)-induced signaling, suggesting that lycopene primarily affects TNF-α-induced NF-κB signaling pathway. In a functional study, lycopene dose-dependently attenuated monocyte adhesion to endothelial monolayer but not that adhesion to extracellular matrix. Taken together, we provided here the first evidence showing that lycopene is able to inhibit TNF-α-induced NF-κB activation, ICAM-1 expression, and monocyte-endothelial interaction, suggesting an anti-inflammatory role of lycopene and possibly explaining in part why lycopene can prevent cardiovascular diseases.