Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion molecule-1 and NF-kappa B-dependent gene expression in human vascular endothelial cells

Monocyte adhesion to the endothelium via adhesion molecules is one of the e arliest events in atherogenesis. It has been suggested that vascular cell a dhesion molecule-1 (VCAM-1) plays a very important role in the recruitment of monocytes in atherosclerosis. The aim of our study was to evaluate wheth er hematein can influence the expression of VCAM-1 and the transcription of nuclear factor-kappaB (NF-kappaB)-dependent genes. Immunohistochemistry re vealed that mouse aortic artery endothelial cells express VCAM-1 after feed ing a high cholesterol diet for 8 weeks. Hematein dose dependently suppress ed TNF-alpha 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 associa ted with a reduction of VCAM-1 mRNA expression. Transient transfection stud y of NF-kappaB promoter construct and electrophoretic mobility shift assay suggested that hematein inhibited both NF-kappaB-dependent gene expression and NF-kappaB activation induced by TNF-alpha. Our results suggest that the down-regulation of VCAM-1 expression by hematein may in part be due to the inhibition of NF-kappaB-dependent gene expression. (C) 2001 Academic Press .