2007 Fiscal Year Final Research Report Summary
Physiological roles of 2-arachidonoylglycerol in inflammation and immunity
| Project/Area Number |
18590074
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Teikyo University |
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Principal Investigator |
SUGIURA Takayuki Teikyo University, Fac. Pharm. Sci, Professor (40130009)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Atsushi Teikyo University, Fac. Pharm. Sci, Associate Professor (80230415)
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| Project Period (FY) |
2006 – 2007
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| Keywords | cannabinoid / 2-arachidonoylglvicerol / anandamide / eosinophil / allergy / macrophage / natural killer / dendritic cell |
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| Research Abstract |
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.
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