2-Arachidonoylglycerol, an Endogenous Cannabinoid Receptor Ligand, Induces Accelerated Production of Chemokines in HL-60 Cells
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概要
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2-Arachidonoylglycerol is an endogenous ligand for the cannabinoid receptors (CB 1 and CB 2). 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 SR 144528, a cannabinoid CB 2 receptor antagonist, indicating that the effect of 2-arachidonoylglycerol is mediated through the CB 2 receptor. Augmented production of interleukin 8 was also observed with CP 55940, 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 CB 2 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.
- 社団法人 日本生化学会の論文
著者
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Oka Saori
Faculty Of Pharmaceutical Sciences Teikyo University
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Waku Keizo
Faculty Of Pharmaceutical Science Teikyo University
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Gokoh Maiko
Faculty Of Pharmaceutical Sciences Teikyo University
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Sugiura Takayuki
Faculty Of Pharmaceutical Sciences Teikyo University
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Kishimoto Seishi
Faculty Of Pharmaceutical Sciences Science University Of Tokyo
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Kobayashi Yuriko
Faculty Of Applied Biological Sciences Gifu University
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