Received for publication June 13, 2007.
Revised September 13, 2007.
Accepted for publication September 13, 2007.

Resveratrol (trans-3,5,4'-trihydroxystilbene) Ameliorates Experimental Allergic Encephalomyelitis (EAE) Primarily via Induction of Apoptosis in T cells Involving Activation of AhR and ER

Abstract

Resveratrol (trans-3,5,4'-trihydroxystilbene), a polyphenolic compound found in plant products including red grapes, exhibits anticancer, antioxidant, and anti-inflammatory properties. Using an animal model of multiple sclerosis (MS), we investigated the use of resveratrol for the treatment of autoimmune diseases. We observed that resveratrol treatment decreased the clinical symptoms and inflammatory responses in Experimental Allergic Encephalomyelitis (EAE)-induced mice. Furthermore, we observed significant apoptosis in inflammatory cells in spinal cord of EAE-induced mice treated with resveratrol when compared to the control mice. Resveratrol administration also led to significant down-regulation of certain cytokines and chemokines in EAE-induced mice including TNF-a, IFN-g, IL-2, IL-9, IL-12, MIP1A, MCP-1, RANTES, and Eotaxin. In vitro studies on the mechanism of action revealed that resveratrol triggered high levels of apoptosis in activated T cells and to a lesser extent in unactivated T cells. Moreover, resveratrol-induced apoptosis was mediated through activation of aryl hydrocarbon receptor (AhR) and estrogen receptor (ER) and correlated with upregulation of AhR, Fas, and FasL expression. Also, resveratrol-induced apoptosis in primary T cells correlated with cleavage of caspase-8, caspase-9, caspase-3, PARP, and release of cytochorme c. Data from the present study, demonstrate for the first time, the ability of resveratrol to trigger apoptosis in activated T cells and its potential use in the treatment of inflammatory and autoimmune diseases including, MS.

Key words: Ah receptor, Apoptosis, Oxidative stress