Lycopene inhibits TNF-alpha-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion.
Inflammatory mediators such as TNF-alpha and interleukin (IL)-1beta, 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 IkappaB phosphorylation, NF-kappaB expression, and NF-kappaB p65 translocation from cytosol to nucleus. In line with this, TNF-alpha-induced NF-kappaB-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-kappaB 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-kappaB 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.
Hung
Chi-Feng
CF
School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan.
Huang
Tur-Fu
TF
Chen
Bing-Huei
BH
Shieh
Jiunn-Min
JM
Wu
Pi-Hui
PH
Wu
Wen-Bin
WB
D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002338:Carotenoids / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D024202:Electrophoretic Mobility Shift Assay; D042783:Endothelial Cells / Q000187:drug effects; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis*; D007371:Interferon-gamma / Q000494:pharmacology; D000077276:Lycopene; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D000975:Antioxidants; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D002338:Carotenoids; D007371:Interferon-gamma; D051550:I-kappa B Kinase; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000077276:Lycopene