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Resveratrol Suppresses Tumor Necrosis Factor--Induced Fractalkine Expression in Endothelial Cells

Renal Regeneration Laboratory and Department of Internal Medicine (S.-O.M., W.K., M.J.S., S.L., K.P.K., D.H.K., S.K.P.), Department of Diagnostic Radiology (S.Y.L.), Research Institute of Clinical Medicine, Chonbuk National University Medical School, Jeonju, Republic of Korea; and Department of Pharmaceutical Engineering, Woosuk University, Jeonju, Republic of Korea (J.-N.S.)

Up-regulation of fractalkine is involved in vascular and tissue damage in inflammatory conditions. Resveratrol has been shown to have anti-inflammatory, antioxidant, and antitumor activities. Its regulatory effects on expression of fractalkine in vascular endothelial cells and fractalkine receptor CX3CR1 in monocytes have not been studied. We evaluated the effects of resveratrol on fractalkine expression in human umbilical vein endothelial cells and CX3CR1 expression in THP-1 cells in response to treatment with tumor necrosis factor (TNF)-. TNF- significantly induced fractalkine mRNA and protein expression in endothelial cells. Resveratrol strongly suppressed TNF--induced fractalkine expression in endothelial cells through suppression of nuclear factor-B and Sp1 activities. Resveratrol decreased the number of TNF--induced fractalkine-positive endothelial cells and CX3CR1-positive cells determined by flow cytometric analysis. Resveratrol suppressed TNF--stimulated monocytes adhesion to human umbilical vein endothelial cells. Immunohistochemical analysis revealed that resveratrol suppressed TNF--induced arterial endothelial fractalkine expression in heart, kidney, and intestine and decreased ED-1-positive cell infiltration in intestinal villi. Resveratrol may provide a new pharmacological approach for suppressing fractalkine/CX3CR1-mediated injury in inflammatory conditions.

Address correspondence to: Dr. Sung Kwang Park, Renal Regeneration Laboratory and Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Keumam-dong, Jeonju, 561-180, Republic of Korea. E-mail: parksk{at}chonbuk.ac.kr

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