Sesamin attenuates intercellular cell adhesion molecule-1 expression in vitro in TNF-α-treated human aortic endothelial cells and in vivo in apolipoprotein-E-deficient mice

Wen-Huey Wu, Shu-Huei Wang, I.-I. Kuan, Ya-S. Kao, Pei-Jhen Wu, Chan-Jung Liang, Hsiung-Fei Chien, Chiu H. Kao, Ching-Jang Huang, Yuh-Lien Chen

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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-α (TNF-α)-treated human aortic endothelial cells (HAECs). When HAECs were pretreated with sesamin (10 or 100 μM), the TNF-α-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 μM). Sesamin and sesamol reduced the marked TNF-α-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-α-stimulated HAECs. Sesamin significantly attenuated TNF-α-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-α -induced extracellular signal-regulated kinase/p38 phosphorylation, nuclear translocation of NF-κB 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. © 2010 WILEY-VCH Verlag GmbH & Co.
Original languageEnglish
Pages (from-to)1340-1350
Number of pages11
JournalMolecular Nutrition and Food Research
Volume54
Issue number9
DOIs
Publication statusPublished - 2010
Externally publishedYes

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Keywords

  • Atherosclerosis
  • Endothelial cell
  • Intercellular cell adhesion molecule-1
  • NF-κb
  • Sesamin
  • 1,3 benzodioxole derivative
  • 1,3 dioxolane derivative
  • antioxidant
  • apolipoprotein E
  • ELAV-like protein 1
  • HuR protein
  • intercellular adhesion molecule 1
  • lignan
  • membrane antigen
  • messenger RNA
  • nonsteroid antiinflammatory agent
  • phenol derivative
  • RNA binding protein
  • sesamin
  • sesamol
  • small interfering RNA
  • tumor necrosis factor alpha
  • animal
  • aorta
  • article
  • atherosclerosis
  • cell culture
  • cell line
  • comparative study
  • cytology
  • drug effect
  • gene expression regulation
  • genetics
  • human
  • metabolism
  • monocyte
  • mouse
  • mouse mutant
  • pathology
  • randomization
  • signal transduction
  • vascular endothelium
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal
  • Antigens, Surface
  • Antioxidants
  • Aorta
  • Apolipoproteins E
  • Benzodioxoles
  • Cell Line
  • Cells, Cultured
  • Dioxoles
  • Endothelium, Vascular
  • Gene Expression Regulation
  • Humans
  • Intercellular Adhesion Molecule-1
  • Lignans
  • Mice
  • Mice, Knockout
  • Monocytes
  • Phenols
  • Random Allocation
  • RNA, Messenger
  • RNA, Small Interfering
  • RNA-Binding Proteins
  • Signal Transduction
  • Tumor Necrosis Factor-alpha
  • Mus
  • Sesamum indicum

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