Julie Gardener
New Member
Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133
in a rodent model of autoimmune uveoretinitis
Heping Xu,*,1,2 Ching L. Cheng,*,†,1in a rodent model of autoimmune uveoretinitis
Mei Chen,* Ayyakkannu Manivannan, ‡ Laurence Cabay,* Roger G. Pertwee,
§ Angela Coutts, § and John V. Forrester*
Departments of *Ophthalmology and ‡ Radiology, School of Medicine, and §
School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom; and † Singapore National Eye Centre, Singapore Eye Research Institute, Singapore
September 1, 2007
Journal of Leukocyte Biology
vol. 82 no. 3 532-541
Abstract: Previous studies have shown that cannabinoids have anti-inflammatory and immunemodulating effects, but the precise mechanisms of action remain to be elucidated. In this study, we investigated the effect of JWH 133, a selective agonist for cannabinoid receptor 2, the main receptor expressed on immune cells, in a model of autoimmune disease, experimental autoimmune uveoretinitis (EAU). JWH 133 suppressed EAU in a dose-dependent manner (0.015–15 mg/kg), and the suppressive effect could be achieved in the disease-induction stage and the effector stage. Leukocytes from mice, which had been treated with JWH 133, had diminished responses to retinal peptide and mitogen Con A stimulation in vitro. In vivo JWH 133 treatment also abrogated leukocyte cytokine/chemokine production. Further in vitro studies indicated that JWH 133 down-regulated the TLR4 via Myd88 signal transduction, which may be responsible for its moderate, suppressive effect on antigen presentation. In vivo JWH 133 treatment (1 mg/kg) also suppressed leukocyte trafficking (rolling and infiltration) in inflamed retina as a result of an effect on reducing adhesion molecules CD162 (P-selectin glycoprotein ligand 1) and CD11a (LFA-1) expression on T cells. In conclusion, the cannabinoid agonist JWH 133 has a high in vivo, anti-inflammatory property and may exert its effect via inhibiting the activation and function of autoreactive T cells and preventing leukocyte trafficking into the inflamed tissue. J. Leukoc. Biol. 82: 532–541; 2007
Source: Anti-inflammatory property of the cannabinoid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis
