Roles of endogenous cannabinoid receptor ligands in acute inflammation and allergic

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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