PMID- 26848215 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20160205 LR - 20200930 IS - 1013-9087 (Print) IS - 2005-3894 (Electronic) IS - 1013-9087 (Linking) VI - 28 IP - 1 DP - 2016 Feb TI - Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model. PG - 22-9 LID - 10.5021/ad.2016.28.1.22 [doi] AB - BACKGROUND: Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation. However, the endogenous modulators for mast cell activation and the underlying mechanism have yet to be elucidated. Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation. OBJECTIVE: In order to investigate the effect of cannabinoid receptor-1 (CB1R) agonists on mast cell activation, AEA-derived compounds were newly synthesized and evaluated for their effect on mast cell activation. METHODS: The effects of selected compounds on FcepsilonRI-induced histamine and beta-hexosaminidase release were evaluated in a rat basophilic leukemia cell line (RBL-2H3). To further investigate the inhibitory effects of CB1R agonist in vivo, an oxazolone-induced atopic dermatitis mouse model was exploited. RESULTS: We found that CB1R inhibited the release of inflammatory mediators without causing cytotoxicity in RBL-2H3 cells and that CB1R agonists markedly and dose-dependently suppressed mast cell proliferation indicating that CB1R plays an important role in modulating antigen-dependent immunoglobulin E (IgE)-mediated mast cell activation. We also found that topical application of CB1R agonists suppressed the recruitment of mast cells into the skin and reduced the level of blood histamine. CONCLUSION: Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis. FAU - Nam, Gaewon AU - Nam G AD - Department of Cosmetic Science and Technology, Seowon University, Cheongju, Korea. FAU - Jeong, Se Kyoo AU - Jeong SK AD - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea. FAU - Park, Bu Man AU - Park BM AD - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea. FAU - Lee, Sin Hee AU - Lee SH AD - CRID Center, NeoPharm Co., Ltd., Daejeon, Korea. FAU - Kim, Hyun Jong AU - Kim HJ AD - Department of Dermatology, Atopy and Asthma Center and Seoul Medical Research Institute, Seoul Medical Center, Seoul, Korea. FAU - Hong, Seung-Phil AU - Hong SP AD - Department of Dermatology, Dankook University Medical College, Cheonan, Korea. FAU - Kim, Beomjoon AU - Kim B AD - Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea. FAU - Kim, Bong-Woo AU - Kim BW AD - Department of Cosmetic Science and Technology, Seowon University, Cheongju, Korea. LA - eng PT - Journal Article DEP - 20160128 PL - Korea (South) TA - Ann Dermatol JT - Annals of dermatology JID - 8916577 PMC - PMC4737832 OTO - NOTNLM OT - Atopic dermatitis OT - Cannabinoid receptor agonists OT - Histamine OT - Mast cells EDAT- 2016/02/06 06:00 MHDA- 2016/02/06 06:01 PMCR- 2016/02/01 CRDT- 2016/02/06 06:00 PHST- 2015/02/02 00:00 [received] PHST- 2015/05/03 00:00 [revised] PHST- 2015/05/06 00:00 [accepted] PHST- 2016/02/06 06:00 [entrez] PHST- 2016/02/06 06:00 [pubmed] PHST- 2016/02/06 06:01 [medline] PHST- 2016/02/01 00:00 [pmc-release] AID - 10.5021/ad.2016.28.1.22 [doi] PST - ppublish SO - Ann Dermatol. 2016 Feb;28(1):22-9. doi: 10.5021/ad.2016.28.1.22. Epub 2016 Jan 28.