Physiological roles of 2-arachidonoylglycerol in inflammation and immunity

2-花生四烯酰甘油在炎症和免疫中的生理作用

• 批准号: 18590074
• 负责人: SUGIURA Takayuki
• 金额: $ 2.57万
• 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: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590074/
• 关键词: cannabinoid; 2-arachidonoylglvicerol; anandamide; eosinophil; allergy; macrophage; natural killer; dendritic cell; 2-アラキドノイルグリセロール; モノアシルグリセロール; アレルギー; マリファナ; 抗炎症薬; 脂質メディエーター; エイコサノイド

In this study, we first examined the roles of the CB2 receptor and 2-AG in allergic inflammation. We found that the level of 2-AG was dramatically augmented in the mouse ear with chronic contact dermatitis. Notably, treatment with SR144528, a CB2 receptor antagonist, markedly reduced allergic inflammation. These results strongly suggest that the CB2 receptor and its endogenous ligand 2-AG are closely involved in allergic inflammation.We then examined the effect of 2-AG on eosinophils. We found that 2-AG augmented the adhesion of human eosinophils to endothelial cells. Interestingly, treatment of the endothelial cells with SR144528 abolished thrombin- or TNF-alpha- induced adhesion of eosinophils to endothelial cells. These results suggest that the CB2 and 2-AG are also involved in the pathogenesis of the vascular system.Notably, 2-AG also induced the migration of dendritic cells. This observation suggests that 2-AG may be involved in the regulation of the immune responses.Interestingly, the cytotoxic activity of natural killer cells was markedly augmented by CB2 receptor agonists such as CP55940 and 2-AG. This finding suggests that the CB2 receptor and its endogenous ligand 2-AG are involved in the regulation of cytotoxicity of natural killer cells and play some roles in the natural immunity.We found that the phagocytic activity of macrophage-like cells was augmented following treat-ment of the cells with 2-AG, indicating that the CB2 receptor and its endogenous ligand 2-AG are also involved in the pathogenesis of inflammatory reactions in various mammalian tissues.These results strongly suggest that the CB2 receptor and its endogenous ligand 2-AG are closely involved in various types of inflammatory reactions and immune responses in mammals.

在这项研究中，我们首先研究了 CB2 受体和 2-AG 在过敏性炎症中的作用。我们发现患有慢性接触性皮炎的小鼠耳朵中 2-AG 的水平显着升高。值得注意的是，用 SR144528（一种 CB2 受体拮抗剂）治疗可显着减少过敏性炎症。这些结果强烈表明CB2受体及其内源性配体2-AG与过敏性炎症密切相关。然后我们检查了2-AG对嗜酸性粒细胞的影响。我们发现 2-AG 增强了人嗜酸性粒细胞与内皮细胞的粘附。有趣的是，用SR144528处理内皮细胞消除了凝血酶或TNF-α诱导的嗜酸性粒细胞与内皮细胞的粘附。这些结果表明CB2和2-AG也参与血管系统的发病机制。值得注意的是，2-AG还诱导树突状细胞的迁移。这一观察结果表明2-AG可能参与免疫反应的调节。有趣的是，CB2受体激动剂如CP55940和2-AG显着增强了自然杀伤细胞的细胞毒活性。这一发现表明CB2受体及其内源性配体2-AG参与自然杀伤细胞的细胞毒性调节，并在自然免疫中发挥一定作用。我们发现用2-AG处理细胞后，巨噬细胞样细胞的吞噬活性增强，表明CB2受体及其内源性配体2-AG也参与炎症的发病机制。 这些结果有力地表明CB2受体及其内源性配体2-AG与哺乳动物各种类型的炎症反应和免疫反应密切相关。

项目成果

An endogenous ligand for GPR55, a G pro-tein-coupled receptor

GPR55（一种 G 蛋白偶联受体）的内源性配体

• 发表时间: 2007
• 作者: Takayuki;Sugiura
• 通讯作者: Sugiura

Identifaction of GPR55 as a lysophosphatidylinositol receptor

GPR55作为溶血磷脂酰肌醇受体的鉴定

• 发表时间: 2007
• 期刊: Biochem.Biophys.Res.Commun. 362
• 作者: Oka;S.;et. al.
• 通讯作者: et. al.

Depolarization-induced rapid generation of 2-arachidonoylglycerol, an endogenous cannabinoid receptor ligand, in rat brain synaptosomes

• DOI: 10.1093/jb/mvm070
• 发表时间: 2007-05-01
• 期刊: JOURNAL OF BIOCHEMISTRY
• 影响因子: 2.7
• 作者: Oka, Saori;Arai, Shunsuke;Sugiura, Takayuki
• 通讯作者: Sugiura, Takayuki

Depolarization-induced rapid generation of 2-arachidonoylglycerol, and endogenous cannabinoid receptor ligand, in rat brain synaptosomes

去极化诱导大鼠脑突触体中 2-花生四烯酰甘油和内源性大麻素受体配体的快速生成

• 发表时间: 2007
• 期刊: J. Biochem 141
• 作者: Oka;S.;et. al.
• 通讯作者: et. al.

An endogenous ligand for GPR55,a G protein-coupled receptor

GPR55 的内源性配体，G 蛋白偶联受体

• 发表时间: 2007
• 作者: Toshihide;Kashihara;Tomohisa;Ishikawa;Koichi;Nakayama;Takayuki Sugiura
• 通讯作者: Takayuki Sugiura