Hematein inhibits tumor necrotic factor-alpha-induced vascular cell adhesion molecule-1 and NF-kappaB-dependent gene expression in human vascular endothelial cells.
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-kappaB (NF-kappaB)-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-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 associated with a reduction of VCAM-1 mRNA expression. Transient transfection study 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.
Genetic Resources Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Yusong, Taejon, 305-600, Korea.
J J
JJ
Hong
T S
TS
Jeong
J H
JH
Choi
J H
JH
Park
K Y
KY
Lee
Y J
YJ
Seo
S R
SR
Oh
G T
GT
Oh
D000818:Animals; D001021:Aortic Valve / Q000378:metabolism; D001161:Arteriosclerosis / Q000235:genetics / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006416:Hematoxylin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006801:Humans; D006949:Hyperlipidemias / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis / Q000235:genetics*
D016328:NF-kappa B; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C007915:hematein; D006416:Hematoxylin