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

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.