Resveratrol inhibits expression and binding activity of the monocyte chemotactic protein-1 receptor, CCR2, on THP-1 monocytes

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• 作者：John P. Cullen ; David Morrow ; Ying Jin ; Nicholas von Offenberg Sweeney ; James V. Sitzmann ; Paul A. Cahill ; Eileen M. Redmond
• 关键词：Resveratrol ; MCP-1 ; CCR2 ; Chemokine receptor ; Monocytes ; Atherosclerosis ; Polyphenol
• 刊名：Atherosclerosis
• 出版年：2007
• 出版时间：November 2007
• 年：2007
• 卷：195
• 期：1
• 页码：e125-e133
• 全文大小：650 K

文摘

Monocyte chemotactic protein-1 and its receptor, CCR2, play a key role in atherosclerosis. We determined the effect of the polyphenol, resveratrol, on CCR2 and the mechanisms involved. Resveratrol treatment inhibited ¹²⁵I-MCP-1 binding to THP-1 cells; 31, 56, 84 % decrease for 10, 50 and 100 μM resveratrol, in the absence of any effect on receptor affinity. The inhibitory effect of resveratrol on ¹²⁵I-MCP-1 binding to THP-1 cells and on CCR2 protein expression determined by FACS analysis was attenuated by treatment with L-NAME (NOS inhibitor), PD98059 (MAPK inhibitor) and LY294002 (PI3K inhibitor), whereas neither X/XO (reactive oxygen species generator) nor ICI182780 (estrogen receptor antagonist) had any effect. Concomitant with a decrease in CCR2 protein expression, resveratrol inhibited THP-1 CCR2 mRNA levels, in the absence of any effect on its stability; 26 and 45 % inhibition at 10 and 50 μM resveratrol, respectively. This effect was not altered by co-treatment with L-NAME, PD98059 or ICI182780, but was potentiated by LY294002 and X/XO. Conclusions: Resveratrol inhibits monocyte CCR2 binding activity in an NO-, MAPK- and PI3K-dependent manner, whereas it inhibits CCR2 mRNA in an NO- and MAPK-independent, PI3K-dependent manner. These inhibitory effects of resveratrol on chemokine receptor binding and expression may contribute, in part, to its cardiovascular protective activity in vivo.