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Activation des cellules Natural Killer par les endocannabinoïdes Anandamide et 2-Arachidonoyl-glycérol

Abstract : Endocannabinoïds, anandamide (AEA) and 2-arachidonoylglycerol (2-AG), belong to the andocannabinoïd system are involved in regulating of many biological systems. They have a role in modulating the immune system and anti-tumor defense. In this study, we show that AEA and 2-AG may modulate the activation of natural killer cells CD56+CD3- (NK) cells and NK92. At low doses , they potentiate the production of IFN gamma induced by suboptimal doses of IL-12, IL-15 and IL-2. In addition, AEA and 2-AG potentiate the cytotoxicity of NK cells. Experiments to quantify transcripts encoding FasL, TRAIL, perforin and granzyme and inhibition experiments indicate that this increase in cytotoxicity was correlated with increased expression of FasL, while production of granzyme, perforin and expression TRAIL remains unchanged. Endocannabinoïd effects on NK cells are inhibited in the presence of antagonist of the type 2 endocannabinoïd receptor (CB2). These in vitro studies have been confirmed in vivo in a murine tumor model. Murine NK cells stimulated ex-vivo by endocannabinoïds and reinjected directly in the tumor, induce a significant slowing of tumor growth. These results show for the first time that endocannabinoïds AEA and 2-AG used at low doses are involved in the modulation of regulatory activities (objectified by the production of IFN gamma) and cytotoxic activities of NK cells.
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Submitted on : Tuesday, June 10, 2014 - 4:33:05 PM
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Thomas Bouachour. Activation des cellules Natural Killer par les endocannabinoïdes Anandamide et 2-Arachidonoyl-glycérol. Immunologie. Université d'Angers, 2012. Français. ⟨tel-01003790⟩

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