title: Genistein suppression of TNF-alpha-induced fractalkine expression in endothelial cells.
abstract: 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.
authors.affiliation: Food Convergence Research Division, Korea Food Research Institute, Songnam, Gyongki-do, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Duk-Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Munkhtugs
authors.initials: M
authors.lastname: Davaatseren
authors.forename: Haeng Jeon
authors.initials: HJ
authors.lastname: Hur
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Yu Jin
authors.initials: YJ
authors.lastname: Jung
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
authors.forename: Dae Young
authors.initials: DY
authors.lastname: Kwon
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000073883:CX3C Chemokine Receptor 1; D002460:Cell Line; D054428:Chemokine CX3CL1 / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D019833:Genistein / Q000494:pharmacology*; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D016588:Anticarcinogenic Agents; D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D008070:Lipopolysaccharides; D016328:NF-kappa B; D019707:Receptors, Chemokine; D014409:Tumor Necrosis Factor-alpha; D019833:Genistein; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases