title: Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model.
abstract: 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 FcεRI-induced histamine and β-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.
  
  
  CONCLUSIONS
  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.
authors: Department of Cosmetic Science and Technology, Seowon University, Cheongju, Korea.
authors: Gaewon
authors: G
authors: Nam
authors: CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
authors: Se Kyoo
authors: SK
authors: Jeong
authors: CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
authors: Bu Man
authors: BM
authors: Park
authors: CRID Center, NeoPharm Co., Ltd., Daejeon, Korea.
authors: Sin Hee
authors: SH
authors: Lee
authors: Department of Dermatology, Atopy and Asthma Center and Seoul Medical Research Institute, Seoul Medical Center, Seoul, Korea.
authors: Hyun Jong
authors: HJ
authors: Kim
authors: Department of Dermatology, Dankook University Medical College, Cheonan, Korea.
authors: Seung-Phil
authors: SP
authors: Hong
authors: Department of Dermatology, Chung-Ang University College of Medicine, Seoul, Korea.
authors: Beomjoon
authors: B
authors: Kim
authors: Department of Cosmetic Science and Technology, Seowon University, Cheongju, Korea.
authors: Bong-Woo
authors: BW
authors: Kim
keywords: Atopic dermatitis; Cannabinoid receptor agonists; Histamine; Mast cells