Moon Sang-Ok, Kim Won, Sung Mi Jeong, Lee Sik, Kang Kyung Pyo, Kim Duk Hoon, Lee Sang Yong, So June-No, Park Sung Kwang
Renal Regeneration Laboratory and Department of Internal Medicine, Chonbuk National University Medical School, San 2-20 Keumam-dong, Jeonju, 561-180, Republic of Korea.
Mol Pharmacol. 2006 Jul;70(1):112-9. doi: 10.1124/mol.106.022392. Epub 2006 Apr 13.
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.
趋化因子的上调参与炎症状态下的血管和组织损伤。白藜芦醇已被证明具有抗炎、抗氧化和抗肿瘤活性。其对血管内皮细胞中趋化因子表达及单核细胞中趋化因子受体CX3CR1的调节作用尚未得到研究。我们评估了白藜芦醇对人脐静脉内皮细胞中趋化因子表达及THP-1细胞中CX3CR1表达的影响，这些细胞是在接受肿瘤坏死因子（TNF）-α处理后做出反应的。TNF-α显著诱导内皮细胞中趋化因子的mRNA和蛋白表达。白藜芦醇通过抑制核因子-κB和Sp1的活性，强烈抑制TNF-α诱导的内皮细胞中趋化因子的表达。通过流式细胞术分析确定，白藜芦醇减少了TNF-α诱导的趋化因子阳性内皮细胞和CX3CR1阳性细胞的数量。白藜芦醇抑制TNF-α刺激的单核细胞与人脐静脉内皮细胞的黏附。免疫组织化学分析显示，白藜芦醇抑制TNF-α诱导的心脏、肾脏和肠道动脉内皮趋化因子表达，并减少肠绒毛中ED-1阳性细胞浸润。白藜芦醇可能为抑制炎症状态下趋化因子/CX3CR1介导的损伤提供一种新的药理学方法。
