We compared the effects of genistein and daidzein on the expression of chemokines, cell adhesion molecules (CAMs), and endothelial nitric oxide synthase (eNOS) in tumor necrosis factor (TNF)-alpha-stimulated human umbilical vascular endothelial cells (HUVECs). TNF-alpha exposure significantly increased expression of monocyte chemoattractant protein (MCP)-1, vascular adhesion molecule (VCAM)-1, and intercellular adhesion molecule-1. Genistein significantly decreased MCP-1 and VCAM-1 production in a dose-dependent manner, whereas CAM expression was not significantly lowered by genistein treatment. However, daidzein slightly decreased MCP-1 production. The effects of genistein and daidzein on MCP-1 secretion coincided with mRNA expression. Pre-treatment with either genistein or daidzein elevated eNOS expression and nitric oxide production disturbed by TNF-alpha exposure. A low concentration of isoflavones significantly inhibited nuclear factor (NF)kappaB activation, whereas a high dose slightly ameliorated these inhibitive effects. These results suggest that genistein had a stronger effect on MCP-1 and eNOS expression than that of daidzein. Additionally, NFkappaB transactivation might be partially related to the down-regulation of these mRNAs in TNF-alpha-stimulated HUVECs.
Cell Adhesion ; Cell Adhesion Molecules ; Chemokines ; Down-Regulation ; Endothelial Cells ; Genistein ; Humans ; Intercellular Adhesion Molecule-1 ; Isoflavones ; Monocytes ; Nitric Oxide ; Nitric Oxide Synthase Type III ; RNA, Messenger ; Transcriptional Activation ; Tumor Necrosis Factor-alpha ; Vascular Cell Adhesion Molecule-1