Roles of endogenous cannabinoid receptor ligands in acute inflammation and allergic

在这项研究中，我们研究了CB 2大麻素受体及其内源性配体2-花生四烯酰甘油（2-AG）在急性炎症和过敏性炎症中可能的病理生理作用。发现2-AG可增强分化为巨噬细胞样细胞的HL-60细胞和人外周血单核细胞与纤连蛋白和VCAM-1的粘附。CB 2受体、Gi/o和PI 3-激酶参与了2-AG增强的细胞粘附.我们发现，在12-O-十四酰佛波醇-13-乙酸酯（TPA）诱导的小鼠耳急性炎症中，2-AG的量显著增加。重要的是，TPA诱导的耳肿胀被CB 2受体拮抗剂SR 144528阻断，表明CB 2受体参与肿胀。有趣的是，将2-AG应用于小鼠耳朵引起肿胀。另一方面，我们证明了合成大麻素受体激动剂WIN 55212 -2抑制了局部应用引起的小鼠耳肿胀 ...更多信息 TPA。提示WIN 55212 -2的抗炎活性是由于干扰内源性配体2-AG的作用。2-AG和2-AG醚（2-AG的醚连接的非水解类似物）被证明可诱导人外周血嗜酸性粒细胞的迁移.用恶唑酮诱导的小鼠耳变应性炎症观察到2-AG的量增加。用SR 144528处理小鼠可抑制恶唑酮诱导的耳肿胀。此外，SR 144528治疗可减弱恶唑酮重复激发诱导的慢性接触性皮炎中嗜酸性粒细胞的募集和耳肿胀。我们还发现，2-AG诱导人类自然杀伤细胞的迁移。与2-AG相反，大麻素和Δ^9-四氢大麻酚未能诱导迁移。这些结果表明CB 2受体和2-AG在急性炎症和过敏性炎症的炎症反应过程中发挥着关键的模拟作用。少

In this study, we investigated possible pathophysiological roles of CB2 cannabinoid receptor and its endogenous ligand, 2-arachidonoylglycerol (2-AG), in acute inflammation and allergic inflammation.1. 2-AG was found to enhance the adhesion of HL-60 cells differentiated into macrophage-like cells and human peripheral blood monocytes to fibronectin and VCAM-1. The CB2 receptor, Gi/o and PI 3-kinase were shown to be involved in 2-AG-augmented cell adhesion.2. We found that the amount of 2-AG was markedly augmented in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute inflammation in 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. Interestingly, the application of 2-AG to the mouse ear evoked swelling. On the other hand, we demonstrated that WIN55212-2, a synthetic cannabinoid receptor agonist, suppressed mouse ear swelling induced by topical application … More TPA. It was suggested that the anti-inflammatory activity of WIN55212-2 is attribute to interference with the actions of the endogenous ligand, 2-AG.3. 2-AG and 2-AG ether, an ether linked nonhydrolysable analog of 2-AG, was shown to induce the migration of human peripheral blood eosinophils.4. Augmentation of the amount of 2-AG was observed with oxazolone-induced allergic inflammation of mouse ear. Oxazolone-induced ear swelling was inhibited by treatment with SR144528 of the mice. Furthermore, treatment with SR144528 attenuated the recruitment of eosinophils and ear swelling in chronic contact dermatitis induced by repeated challenge with oxazolone.5. We also found that 2-AG induces the migration of human natural killer cells. In contrast to 2-AG, anandamide and Δ^9-tetrahydrocannabinol failed to induce the migration.These results suggest that the CB2 receptor and 2-AG play crucial simulative roles during the course of inflammatory reactions in acute inflammation and allergic inflammation. Less