Anti-inflammatory property of the cannaboinid receptor-2-selective agonist JWH-133 in a rodent model of autoimmune uveoretinitis

Heping Xu, Ching L. Cheng, Mei Chen, Ayyakkannu Manivannan, Laurence Cabay, Roger Guy Pertwee, Angela Alice Coutts, John Vincent Forrester

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80 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)532-541
Number of pages10
JournalJournal of Leukocyte Biology
Volume82
Issue number3
Early online date30 May 2007
DOIs
Publication statusPublished - 1 Sep 2007

Keywords

  • antigen presentation
  • autoimmunity
  • leukocyte trafficking
  • macrophage costimulatory activity
  • legionella-pneumophila infection
  • stable antigen-expression
  • dendritic cells
  • CB2 receptor
  • T-lymphocytes
  • viral-10
  • P-selectin
  • activation
  • mice

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