Journal of Leukocyte Biology Myeloid cells, immune suppression, tumor immunology
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A more recent version of this article appeared on September 1, 2007

Published online before print May 30, 2007
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0307159

Received for publication March 14, 2007.
Revised April 20, 2007.
Accepted for publication April 23, 2007.

Article

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

Heping Xu *@, Ching L. Cheng *{dagger}, Mei Chen *, Ayyakkannu Manivannan {ddagger}, Laurence Cabay *, Roger G. Pertwee {sect}, Angela Coutts {sect}, and John V. Forrester *

Departments of *Ophthalmology and {ddagger}Radiology, School of Medicine, and {sect}School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom; and {dagger}Singapore National Eye Centre, Singapore Eye Research Institute, Singapore

@ To whom correspondence should be addressed. E-mail: h.xu{at}abdn.ac.uk.


  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.

Key Words: antigen presentation • autoimmunity • leukocyte trafficking






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Copyright © 2007 by the Society for Leukocyte Biology.