CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents
CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: Potential role for CB2-selective ligands as immunosuppressive agents
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DOI：
10.1016/j.clim.2006.11.002
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发表时间：
2007-03-01
影响因子：
8.6
通讯作者：
Nagarkatti, Prakash
中科院分区：
文献类型：
--
作者：
Lombard, Catherine;Nagarkatti, Mitzi;Nagarkatti, Prakash
已知大麻素可分别与神经系统和免疫系统中表达的CB1和CB2受体相互作用，并介导一系列的作用，包括抗炎特性。然而，结合CB1的大麻素也具有精神活性，因此限制了它们的临床应用。在本研究中，我们研究了人工合成的CB2选择性激动剂JWH-015的免疫抑制特性。我们发现JWH-015在体外诱导胸腺细胞凋亡，并通过诱导凋亡抑制T、B细胞对有丝分裂原的增殖反应。JWH-015可诱导caspase-8、caspase-9、caspase-3等外源性和内源性细胞凋亡途径之间的串扰以及线粒体膜电位的丧失。最后，体内注射JWH-015可导致胸腺萎缩、细胞凋亡，并降低外周T细胞对有丝分裂原的反应。总之，这项研究表明，CB2选择性激动剂，没有精神药物作用，可能作为新的抗炎/免疫抑制药物。(C)2006 Elsevier Inc.保留所有权利。
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.