期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 586, 期 1-3, 页码 275-282出版社
ELSEVIER
DOI: 10.1016/j.ejphar.2008.03.001
关键词
adhesion molecule; atherosclerosis; cytokine; inflammation; natural product; tomato
Inflammatory mediators such as TNF-alpha and interleukin (IL)-1 beta, 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-alpha-induced signaling in human umbilical endothelial cells (HUVECs). We found that TNF-alpha-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-alpha-induced I kappa B phosphorylation, NF-kappa B expression, and NF-kappa B p65 translocation from cytosol to nucleus. In line with this, TNF-alpha-induced NF-kappa B-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-alpha-induced p38 and extracellular matrix-regulated kinase1/2 (ERK1/2) phosphorylation and interferon-gamma (IFN-gamma)induced signaling, suggesting that lycopene primarily affects TNF-alpha-induced NF-kappa B 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-alpha-induced NF-kappa B 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. (c) 2008 Elsevier B.V. All rights reserved.
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