期刊
CLINICAL IMMUNOLOGY
卷 122, 期 3, 页码 259-270出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.clim.2006.11.002
关键词
Cannabinoids; CB2 receptor; immunosuppression; apoptosis; anti-inflammatory agent; non-psychoactive agent
类别
资金
- NHLBI NIH HHS [R01 HL058641, R01-HL058641] Funding Source: Medline
- NIAID NIH HHS [R01 AI053703, R01-AI058300, R01-AI53703, R01 AI058300] Funding Source: Medline
- NIDA NIH HHS [R21-DA014885, R01-DA016545, R01 DA016545] Funding Source: Medline
- NIEHS NIH HHS [R01-ES09098, R01 ES009098] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL058641] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R01AI053703, R01AI058300] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES [R01ES009098] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON DRUG ABUSE [R01DA016545, R21DA014885] Funding Source: NIH RePORTER
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. (c) 2006 Elsevier Inc. All rights reserved.
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