文章基本信息

标题：The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages
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作者：Ming-xiu Hao ; Li-sheng Jiang ; Ning-yuan Fang 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2010
卷号：51
期号：8
页码：2181-2190
DOI：10.1194/jlr.M001511
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：The endocannabinoid system has recently been attracted interest for its anti-inflammatory and anti-oxidative properties. In this study, we investigated the role of the endocannabinoid system in regulating the oxidized low-density lipoprotein (oxLDL)-induced inflammatory response in macrophages. RAW264.7 mouse macrophages and peritoneal macrophages isolated from Sprague-Dawley (SD) rats were exposed to oxLDL with or without the synthetic cannabinoid WIN55,212-2. To assess the inflammatory response, reactive oxygen species (ROS) and tumor necrosis factor alpha (TNF- α) levels were determined, and activation of the mitogen-activated protein kinase (MAPK) and nuclear factor (NF)-kappa B signaling pathways were assessed. We observed that: i ) oxLDL strongly induced ROS generation and TNF- α secretion in murine macrophages; ii ) oxLDL-induced TNF- α and ROS levels could be lowered considerably by WIN55,212-2 via inhibition of MAPK (ERK1/2) signaling and NF-kappa B activity; and iii ) the effects of WIN55212-2 were attenuated by the selective CB2 receptor antagonist AM630. These results demonstrate the involvement of the endocannabinoid system in regulating the oxLDL-induced inflammatory response in macrophages, and indicate that the CB2 receptor may offer a novel pharmaceutical target for treating atherosclerosis.
关键词：atherosclerosis ; TNF-α ; ROS ; inflammatory response ; CB2 receptor ; oxLDL