Genistein Suppression of TNF-α-induced Fractalkine Expression in Endothelial Cells

Genistein is a polyphenolic nonsteroidal isoflavonoid with estrogen-like activity has been shown to have anticancer, antioxidant, and anti-inflammatory activities. Fractalkine is a unique chemokine that functions as a chemoattractant and an adhesion molecule on endothelial cells activated by proinflammatory cytokines. In this study, we investigated the effects of genistein (5-25 muM) on fractalkine expression in human umbilical vein endothelial cells (HUVECs) and on its receptor, CX3CR1, in THP-1 cells in response to treatment with tumor necrosis factor (TNF)- alpha. TNF-alpha significantly induced fractalkine expression in endothelial cells. Genistein decreased TNF-alpha-induced fractalkine expression through suppression of Akt and p38 phosphorylation and NF-kappaB activities. Genistein also strongly suppressed TNF-alpha-induced expression of CX3CR1 in monocytes. Genistein suppressed TNF-alpha-stimulated adhesion of monocytes to HUVECs. Immunohistochemical analysis revealed that genistein suppressed the in vivo lipopolysaccharide (LPS)-induced arterial endothelial fractalkine expression in the heart, kidney, and small intestine. These results suggest that genistein may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury under vascular inflammatory conditions.