Physiological roles of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand

内源性大麻素受体配体 2-花生四烯酰甘油的生理作用

• 批准号: 16590063
• 负责人: SUGIURA Takayuki
• 金额: $ 2.24万
• 依托单位: Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590063/
• 关键词: Cannabinoid; 2-Arachidonoylglycerol; Inflammation; Immunity; CB2 receptor; Nitric oxide; Adhesion; CB2受容体; アナンダミド; 好酸球; NO

In this study, we first investigated possible pathophysiological roles of the CB2 receptor and 2-AG in acute inflammation in mouse ear induced by the topical application of TPA. We found that the amount of 2-AG was markedly augmented in inflamed mouse ear. Importantly, TPA-induced ear swelling was blocked by treatment with SR144528, a CB2 receptor antagonist, suggesting that the CB2 receptor is involved in the swelling. The application of SR144528 also reduced the TPA-induced production of LTB_4 and the infiltration of neutrophils in the mouse ear. Similar results observed with oxazolone-induced allergic inflammation in mouse ear. Interestingly, the application of 2-AG to the mouse ear evoked swelling, which was abolished by treatment with SR144528. Nitric oxide was suggested to be involved in the ear swelling induced by 2-AG. These results suggest that the CB2 receptor and 2-AG play crucial stimulative roles during the course of inflammatory reactions.We next examined the effect of 2-AG on the adhesion of HL-60 cells differentiated into macrophage-like cells. We found that 2-AG enhanced the adhesion of differentiated HL-60 cells to fibronectin and VCAM-1. The CB2 receptor, Gi/Go and PI 3-kinase were shown to be involved in 2-AG-induced augmented cell adhesion. 2-AG also enhanced the adhesion of human monocytic leukemia U937 cells and peripheral blood monocytes. These results strongly suggest that 2-AG plays some essential role in inflammatory reactions and immune responses by inducing robust adhesion to extracellular matrix proteins and adhesion molecules in several types of inflammatory cells and immune-competent cells.

在本研究中，我们首先研究了 CB2 受体和 2-AG 在局部应用 TPA 引起的小鼠耳急性炎症中可能的病理生理学作用。我们发现发炎的小鼠耳朵中 2-AG 的量显着增加。重要的是，TPA 引起的耳朵肿胀可以通过 SR144528（一种 CB2 受体拮抗剂）治疗来阻止，这表明 CB2 受体参与了肿胀。 SR144528的应用还减少了TPA诱导的LTB_4的产生以及小鼠耳朵中中性粒细胞的浸润。在恶唑酮诱导的小鼠耳过敏性炎症中观察到类似的结果。有趣的是，将 2-AG 应用于小鼠耳朵会引起肿胀，但通过 SR144528 治疗消除了肿胀。一氧化氮被认为与 2-AG 引起的耳肿胀有关。这些结果表明CB2受体和2-AG在炎症反应过程中发挥着至关重要的刺激作用。接下来我们研究了2-AG对分化为巨噬细胞样细胞的HL-60细胞粘附的影响。我们发现 2-AG 增强分化的 HL-60 细胞对纤连蛋白和 VCAM-1 的粘附。 CB2 受体、Gi/Go 和 PI 3-激酶被证明参与 2-AG 诱导的细胞粘附增强。 2-AG还增强人单核细胞白血病U937细胞与外周血单核细胞的粘附。这些结果强烈表明，2-AG 通过诱导多种类型炎症细胞和免疫活性细胞中细胞外基质蛋白和粘附分子的牢固粘附，在炎症反应和免疫反应中发挥重要作用。

项目成果

2-Arachidonoylglycerol, an endogenous cannabinoid receptor ligand, enhances the adhesion of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes

• DOI: 10.1016/j.febslet.2005.10.030
• 发表时间: 2005-11-21
• 期刊: FEBS LETTERS
• 影响因子: 3.5
• 作者: Gokoh, M;Kishimoto, S;Sugiura, T
• 通讯作者: Sugiura, T

2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces accelerated production of chemokines in HL-60 cells

• DOI: 10.1093/jb/mvh063
• 发表时间: 2004-04-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Kishimoto, S;Kobayashi, Y;Sugiura, T
• 通讯作者: Sugiura, T

2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces the migration of EoL-1 human eosinophilic leukemia cells and human peripheral blood eosinonhils.

2-花生四烯酰甘油是一种内源性大麻素受体配体，可诱导 EoL-1 人嗜酸性粒细胞白血病细胞和人外周血嗜酸性粒细胞的迁移。

• 发表时间: 2004
• 期刊: J. Leukoc. Biol. 76
• 作者: Nobuyuki Kuramoto;Keita Kubo;Kiyokazu Ogita et al.;Saori Oka et al.
• 通讯作者: Saori Oka et al.

Evidence for the involvement of the cannabinoid C132 receptor and its endogenous ligand 2-arachidonoylglycerol in 12-O-tetradecanoyl-phorbol-13-acetate-induced acute inflammation in mouse ear.

大麻素 C132 受体及其内源性配体 2-花生四烯酰甘油参与 12-O-十四烷酰基-佛波醇-13-乙酸酯诱导的小鼠耳急性炎症的证据。

• 发表时间: 2005
• 期刊: J. B,ol. Chem. 280
• 作者: Saor;Oka et al.
• 通讯作者: Oka et al.

2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, induces the migration of EoL-1 human eosinophilic leukemia cells and human peripheral blood eosinophils.

2-花生四烯酰甘油是一种内源性大麻素受体配体，可诱导 EoL-1 人嗜酸性粒细胞白血病细胞和人外周血嗜酸性粒细胞的迁移。

• 发表时间: 2004
• 期刊: J.Leukoc.Biol. 76
• 作者: Oka;S.et al.
• 通讯作者: S.et al.