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The cannabinoid WIN55,212-2 protects against oxidized LDL-induced inflammatory response in murine macrophages

2010; Elsevier BV; Volume: 51; Issue: 8 Linguagem: Inglês

10.1194/jlr.m001511

1539-7262

Mingxiu Hao, Li-Sheng Jiang, Ningyuan Fang, Jun Pu, Liuhua Hu, Linghong Shen, Wei Song, Ben He,

Dietary Effects on Health

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- alpha) 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- alpha secretion in murine macrophages; ii) oxLDL-induced TNF- alpha 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.