Hung C.-F.TUR-FU HUANGChen B.-H.Shieh J.-M.Wu P.-H.Wu W.-B.2021-05-312021-05-312008142999https://scholars.lib.ntu.edu.tw/handle/123456789/564140Inflammatory 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. ? 2008 Elsevier B.V. All rights reserved.[SDGs]SDG3CD31 antigen; cyclooxygenase 2; DNA; gamma interferon; I kappa B; immunoglobulin enhancer binding protein; intercellular adhesion molecule 1; lycopene; mitogen activated protein kinase 1; mitogen activated protein kinase 3; synaptophysin; transcription factor AP 1; transcription factor RelA; tumor necrosis factor alpha; antiinflammatory activity; article; atherosclerosis; cell adhesion; cell nucleus; complex formation; controlled study; cytosol; dose response; drug effect; drug mechanism; endothelium cell; extracellular matrix; gel mobility shift assay; heart protection; human; human cell; monocyte; pharmacodynamics; priority journal; protein expression; protein phosphorylation; protein transport; signal transduction; Antioxidants; Blotting, Western; Carotenoids; Cell Adhesion; Cell Survival; Cells, Cultured; Electrophoretic Mobility Shift Assay; Endothelial Cells; Humans; I-kappa B Kinase; Intercellular Adhesion Molecule-1; Interferon Type II; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Monocytes; p38 Mitogen-Activated Protein Kinases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Signal Transduction; Tumor Necrosis Factor-alpha; Vascular Cell Adhesion Molecule-1journal article10.1016/j.ejphar.2008.03.001184395782-s2.0-43549100851