title: Resveratrol suppresses tumor necrosis factor-alpha-induced fractalkine expression in endothelial cells.
abstract: 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)-alpha. TNF-alpha significantly induced fractalkine mRNA and protein expression in endothelial cells. Resveratrol strongly suppressed TNF-alpha-induced fractalkine expression in endothelial cells through suppression of nuclear factor-kappaB and Sp1 activities. Resveratrol decreased the number of TNF-alpha-induced fractalkine-positive endothelial cells and CX3CR1-positive cells determined by flow cytometric analysis. Resveratrol suppressed TNF-alpha-stimulated monocytes adhesion to human umbilical vein endothelial cells. Immunohistochemical analysis revealed that resveratrol suppressed TNF-alpha-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.
authors.affiliation: Renal Regeneration Laboratory and Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Keumam-dong, Jeonju, 561-180, Republic of Korea.
authors.forename: Sang-Ok
authors.initials: SO
authors.lastname: Moon
authors.forename: Won
authors.initials: W
authors.lastname: Kim
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Sung
authors.forename: Sik
authors.initials: S
authors.lastname: Lee
authors.forename: Kyung Pyo
authors.initials: KP
authors.lastname: Kang
authors.forename: Duk Hoon
authors.initials: DH
authors.lastname: Kim
authors.forename: Sang Yong
authors.initials: SY
authors.lastname: Lee
authors.forename: June-No
authors.initials: JN
authors.lastname: So
authors.forename: Sung Kwang
authors.initials: SK
authors.lastname: Park
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D015153:Blotting, Western; D000073883:CX3C Chemokine Receptor 1; D002448:Cell Adhesion / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C / Q000235:genetics* / Q000378:metabolism; D053331:Ectodysplasins; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000166:cytology / Q000187:drug effects; D007668:Kidney / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D008871:Microvilli / Q000737:chemistry / Q000187:drug effects; D009000:Monocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019707:Receptors, Chemokine / Q000378:metabolism; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048069:Tumor Necrosis Factors / Q000032:analysis
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000073883:CX3C Chemokine Receptor 1; C515538:CX3CL1 protein, human; C095235:CX3CR1 protein, human; D054428:Chemokine CX3CL1; D020523:Chemokines, CX3C; C515540:Cx3cl1 protein, rat; C506018:EDA protein, human; D053331:Ectodysplasins; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D013267:Stilbenes; D014409:Tumor Necrosis Factor-alpha; D048069:Tumor Necrosis Factors; D000077185:Resveratrol