2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells
2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells
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DOI：
10.1093/jb/mvh063
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发表时间：
2004-04-01
影响因子：
2.7
通讯作者：
Sugiura, T
中科院分区：
文献类型：
--
作者：
Kishimoto, S;Kobayashi, Y;Sugiura, T
2-花生四烯酰甘油是大麻素受体（CB 1和CB 2）的内源性配体。以前，我们提供的证据表明，2-花生四烯酰甘油，但不是花生四烯酰胺（N-花生四烯酰乙醇胺），是大麻素受体的真正的天然配体。在本研究中，我们详细研究了2-花生四烯酸甘油对人早幼粒细胞白血病HL-60细胞趋化因子产生的影响。我们发现，2-花生四烯酸甘油诱导白细胞介素8的生产显着加速。用大麻素CB 2受体拮抗剂SR 144528处理细胞可阻断2-花生四烯酸甘油的作用，表明2-花生四烯酸甘油的作用是通过CB 2受体介导的。用CP 55940（一种合成大麻素）和醚连接的2-花生四烯酰甘油类似物也观察到白细胞介素8的产生增加。另一方面，花生四烯酸和花生四烯酸都不能诱导白细胞介素8的产生。在巨噬细胞趋化蛋白-1的产生的情况下，观察到2-花生四烯酸甘油的类似效果。2-花生四烯酰甘油不仅在未分化的HL-60细胞中，而且在分化为巨噬细胞样细胞的HL-60细胞中也观察到白细胞介素8的加速产生。值得注意的是，2-花生四烯酰甘油和脂多糖协同作用，诱导白细胞介素8的产生显着增加。这些结果有力地表明，CB 2受体及其生理配体，即，2-花生四烯酰甘油发挥重要的调节作用，如刺激炎症细胞和免疫活性细胞中趋化因子的产生。因此，对大麻素受体系统的详细研究对于更好地了解炎症反应和免疫反应的精确调节机制至关重要。
2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB1 and CB2). Previously, we provided evidence that 2-arachidonoylglycerol, but not anandamide (N-arachidonoylethanolamine), is the true natural ligand for the cannabinoid receptors. In the present study, we examined in detail the effects of 2-arachidonoylglycerol on the production of chemokines in human promyelocytic leukemia HL-60 cells. We found that 2-arachidonoylglycerol induced a marked acceleration in the production of interleukin 8. The effect of 2-arachidonoylglycerol was blocked by treatment of the cells with SR144528, a cannabinoid CB2 receptor antagonist, indicating that the effect of 2-arachidonoylglycerol is mediated through the CB2 receptor. Augmented production of interleukin 8 was also observed with CP55940, a synthetic cannabinoid, and an ether-linked analog of 2-arachidonoylglycerol. On the other hand, neither anandamide nor the free arachidonic acid induced the enhanced production of interleukin 8. A similar effect of 2-arachidonoylglycerol was observed in the case of the production of macrophage-chemotactic protein-1. The accelerated production of interleukin 8 by 2-arachidonoylglycerol was observed not only in undifferentiated HL-60 cells, but also in HL-60 cells differentiated into macrophage-like cells. Noticeably, 2-arachidonoylglycerol and lipopolysaccharide acted synergistically to induce the dramatically augmented production of interleukin 8. These results strongly suggest that the CB2 receptor and its physiological ligand, i.e., 2-arachidonoylglycerol, play important regulatory roles such as stimulation of the production of chemokines in inflammatory cells and immune-competent cells. Detailed studies on the cannabinoid receptor system are thus essential to gain a better understanding of the precise regulatory mechanisms of inflammatory reactions and immune responses.