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

J Leukoc Biol. 2007 Sep;82(3):532-41. doi: 10.1189/jlb.0307159. Epub 2007 May 30.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Antigen-Presenting Cells / immunology
  • Bone Marrow / immunology
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Cannabinoids / pharmacology*
  • Cell Proliferation / drug effects
  • Chemotaxis, Leukocyte
  • Cytokines / metabolism
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism
  • Flow Cytometry
  • Mice
  • Mice, Inbred BALB C
  • Myeloid Differentiation Factor 88 / metabolism
  • Nervous System Autoimmune Disease, Experimental / drug therapy
  • Nervous System Autoimmune Disease, Experimental / immunology*
  • Nervous System Autoimmune Disease, Experimental / physiopathology
  • Receptor, Cannabinoid, CB2 / agonists*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Retinitis / drug therapy*
  • Retinitis / immunology
  • Signal Transduction
  • T-Lymphocyte Subsets / immunology
  • Toll-Like Receptor 4 / metabolism
  • Uveitis / drug therapy*
  • Uveitis / immunology

Substances

  • Anti-Inflammatory Agents
  • Cannabinoids
  • Cytokines
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Receptor, Cannabinoid, CB2
  • Toll-Like Receptor 4
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC