Abstract
Sesame lignans have antioxidative and anti-inflammatory properties. We focused on the effects of the lignans sesamin and sesamol on the expression of endothelial-leukocyte adhesion molecules in tumor necrosis factor-alpha (TNF-alpha)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 microM), the TNF-alpha-induced expression of intercellular cell adhesion molecule-1 (ICAM-1) was significantly reduced (35 or 70% decrease, respectively) by Western blotting. Sesamol was less effective at inhibiting ICAM-1 expression (30% decrease at 100 microM). Sesamin and sesamol reduced the marked TNF-alpha-induced increase in human antigen R (HuR) translocation and the interaction between HuR and the 3'UTR of ICAM-1 mRNA. Both significantly reduced the binding of monocytes to TNF-alpha-stimulated HAECs. Sesamin significantly attenuated TNF-alpha-induced ICAM-1 expression and cell adhesion by downregulation of extracellular signal-regulated kinase 1/2 and p38. Furthermore, in vivo, sesamin attenuated intimal thickening and ICAM-1 expression seen in aortas of apolipoprotein-E-deficient mice. Taken together, these data suggest that sesamin inhibits TNF-alpha-induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-kappaB p65, cytoplasmic translocalization of HuR and thereby suppresses ICAM-1 expression, resulting in reduced adhesion of leukocytes. These results also suggest that sesamin may prevent the development of atherosclerosis and inflammatory responses.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anti-Inflammatory Agents, Non-Steroidal / pharmacology
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Anti-Inflammatory Agents, Non-Steroidal / therapeutic use
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Antigens, Surface / genetics
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Antigens, Surface / metabolism
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Antioxidants / pharmacology
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Antioxidants / therapeutic use
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Aorta / cytology
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Aorta / drug effects*
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Aorta / metabolism
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Aorta / pathology
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Apolipoproteins E / genetics
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Atherosclerosis / metabolism
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Atherosclerosis / pathology
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Atherosclerosis / prevention & control*
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Benzodioxoles / pharmacology
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Cell Line
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Cells, Cultured
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Dioxoles / pharmacology*
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Dioxoles / therapeutic use*
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ELAV Proteins
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ELAV-Like Protein 1
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects*
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Endothelium, Vascular / metabolism
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Endothelium, Vascular / pathology
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Gene Expression Regulation / drug effects*
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Humans
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Intercellular Adhesion Molecule-1 / genetics
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Intercellular Adhesion Molecule-1 / metabolism*
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Lignans / pharmacology*
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Lignans / therapeutic use*
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Mice
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Mice, Knockout
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Monocytes / drug effects
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Phenols / pharmacology
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RNA, Messenger / metabolism
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RNA, Small Interfering
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RNA-Binding Proteins / genetics
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RNA-Binding Proteins / metabolism
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Random Allocation
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Signal Transduction / drug effects
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Tumor Necrosis Factor-alpha / pharmacology
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antigens, Surface
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Antioxidants
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Apolipoproteins E
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Benzodioxoles
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Dioxoles
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ELAV Proteins
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ELAV-Like Protein 1
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ELAVL1 protein, human
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Lignans
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Phenols
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RNA, Messenger
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RNA, Small Interfering
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RNA-Binding Proteins
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Tumor Necrosis Factor-alpha
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Intercellular Adhesion Molecule-1
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sesamol
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sesamin