Biochemical and Biophysical Research Communications, vol. 281, no. 5, pp. 1127-1133
Monocyte adhesion to the endothelium via adhesion molecules is one of the earliest events in atherogenesis. It has been suggested that vascular cell adhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of monocytes in atherosclerosis. The aim of our study was to evaluate whether hematein can influence the expression of VCAM-1 and the transcription of nuclear factor-κB (NF-κB)-dependent genes. Immunohistochemistry revealed that mouse aortic artery endothelial cells express VCAM-1 after feeding a high cholesterol diet for 8 weeks. Hematein dose dependently suppressed TNF-α-induced VCAM-1 in both surface (30.8%) and soluble protein (65%) production in HUVECs. The transcription level of VCAM-1 was measured by Northern blot analysis, and decreased VCAM-1 protein expression was associated with a reduction of VCAM-1 mRNA expression. Transient transfection study of NF-κB promoter construct and electrophoretic mobility shift assay suggested that hematein inhibited both NF-κB-dependent gene expression and NF-κB activation induced by TNF-α. Our results suggest that the down-regulation of VCAM-1 expression by hematein may in part be due to the inhibition of NF-κB-dependent gene expression.