CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: potential role for CB2-selective ligands as immunosuppressive agents |
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Authors: | Lombard Catherine Nagarkatti Mitzi Nagarkatti Prakash |
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Affiliation: | Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, 6311 Garners Ferry Road, Building 28, Columbia, SC 29208, USA. |
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Abstract: | Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties. However, cannabinoids that bind CB1 are also psychoactive thereby limiting their clinical use. In this study, we investigated the immunosuppressive properties of JWH-015, a synthetic CB2-selective agonist. We found that JWH-015 triggered apoptosis in thymocytes in vitro and inhibited the proliferative response of T and B cells to mitogens through induction of apoptosis. JWH-015 induced cross-talk between extrinsic and intrinsic pathways of apoptosis involving caspase-8, caspase-9, and caspase-3 as well as loss of mitochondrial membrane potential. Finally, administration of JWH-015 in vivo caused thymic atrophy, apoptosis, and decreased peripheral T cell response to mitogens. Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents. |
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Keywords: | Cannabinoids CB2 receptor Immunosuppression Apoptosis Anti-inflammatory agent Non-psychoactive agent |
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