期刊
PHARMACOLOGY
卷 99, 期 5-6, 页码 259-267出版社
KARGER
DOI: 10.1159/000455916
关键词
S-777469; Cannabinoid type 2 receptor; 2-Arachidonoylglycerol; Inflammation; Dermatitis
We investigated the effects of S-777469 (1-[[6-Ethyl-1-[4fluorobenzyl]- 5-methyl-2-oxo-1, 2-dihydropyridine-3-carbonyl] amino]-cyclohexanecarboxylic acid), a novel cannabinoid type 2 receptor (CB2) agonist, on 1-fluoro-2,4-dinitrobenzene (DNFB)-induced ear inflammation and mite antigen-induced dermatitis in mice. The oral administration of S-777469 significantly suppressed DNFB-induced ear swelling in a dose-dependent manner. In addition, S-777469 significantly alleviated mite antigen-induced atopic dermatitis- like skin lesions in NC/Nga mice. A histological analysis revealed that S-777469 significantly reduced the epidermal thickness and the number of mast cells infiltrating skin lesions. We demonstrated that S-777469 inhibited mite antigen-induced eosinophil accumulation in skin lesions and an endogenous CB2 ligand, 2-arachidonoylglycerol (2-AG)-induced eosinophil migration in vitro. Moreover, we confirmed that 2-AG levels significantly increased in skin lesions of mite antigen-induced dermatitis model. Together, these results suggest that S-777469 inhibits skin inflammation in mice by blocking the activities of 2-AG. (C) 2017 S. Karger AG, Basel
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