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Anti‐inflammatory property of the cannabinoid receptor‐2‐selective agonist JWH‐133 in a rodent model of autoimmune uveoretinitis
Author(s) -
Xu Heping,
Cheng Ching L.,
Chen Mei,
Manivannan Ayyakkannu,
Cabay Laurence,
Pertwee Roger G.,
Coutts Angela,
Forrester John V.
Publication year - 2007
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0307159
Subject(s) - cannabinoid , agonist , biology , chemokine , immune system , in vivo , cannabinoid receptor , receptor , pharmacology , inflammation , gpr18 , immunology , biochemistry , microbiology and biotechnology
Previous studies have shown that cannabinoids have anti‐inflammatory and immune‐modulating 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.