Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.
Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.
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DOI：
10.1016/j.imbio.2009.04.001
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发表时间：
2010-08
期刊：
影响因子：
2.8
通讯作者：
Nagarkatti, Prakash
中科院分区：
文献类型：
--
作者：
Rieder, Sadiye Amcaoglu;Chauhan, Ashok;Singh, Ugra;Nagarkatti, Mitzi;Nagarkatti, Prakash
大麻素是存在于大麻植物（Cannabis sativa L.）中的一组化合物。它们通过激活特定的大麻素受体来介导其生理和行为效应。随着大麻素受体（CB1和CB2）和内源性大麻素系统的发现，该领域的研究呈指数级增长。大麻素已被证明是有效的免疫抑制剂和抗炎剂，并已被证明在广泛的免疫介导的疾病，如多发性硬化症，糖尿病，脓毒性休克，类风湿性关节炎和过敏性哮喘中介导有益的作用。大麻素受体1（CB1）主要在中枢神经系统的细胞上以及外周中表达。相反，大麻素受体2（CB2）主要在免疫细胞上表达。大麻素介导免疫抑制的确切机制现在才开始被理解，并且可以大致分为四种途径：细胞凋亡，增殖抑制，细胞因子和趋化因子产生的抑制以及T调节细胞（T细胞）的诱导。我们实验室的研究集中在天然和合成大麻素通过激活CB2受体诱导细胞凋亡的机制上。在这篇综述中，我们将重点关注大麻素介导的免疫抑制对不同免疫细胞群的凋亡机制，并讨论如何激活CB2提供了一种新的治疗方式对炎症和自身免疫性疾病以及免疫系统的恶性肿瘤，而不施加不利的精神影响。
Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially. Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma. Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood and can be broadly categorized into four pathways: apoptosis, inhibition of proliferation, suppression of cytokine and chemokine production and induction of T regulatory cells (T regs). Studies from our laboratory have focused on mechanisms of apoptosis induction by natural and synthetic cannabinoids through activation of CB2 receptors. In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects.
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