Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: Role of CB1/CB2 receptors
Beneficial effects of cannabinoids (CB) in a murine model of allergen-induced airway inflammation: Role of CB1/CB2 receptors
复制标题
DOI：
10.1016/j.imbio.2010.09.004
复制
发表时间：
2011-04-01
期刊：
影响因子：
2.8
通讯作者：
Mempel, Martin
中科院分区：
文献类型：
--
作者：
Braun, Andrea;Engel, Tabea;Mempel, Martin
内源性大麻素系统（ECS）由两种大麻素（CB）受体，即CB 1和CB 2受体，以及与这些受体结合的内源性（内源性大麻素）和外源性（大麻素，例如δ-9-四氢大麻酚（THC））配体组成。基于提示THC和ECS在炎症中的作用的研究，本研究的目的是使用变应性气道炎症的小鼠模型来检查它们在I型超敏反应中的参与。C57 BL/6野生型小鼠的THC治疗显著降低了气道炎症，如通过支气管肺泡灌洗（BAL）中显著降低的总细胞计数所确定的。当小鼠在致敏和激发阶段同时接受治疗时，这些影响最大。此外，在致敏阶段接受THC的小鼠中，全身免疫应答被显著抑制。为了研究CB 1/2受体在这种情况下的作用，我们使用选择性拮抗剂以及CB 1/CB 2受体双敲除小鼠（CB 1-/-/CB 2-/-）对CB 1和/或CB 2受体进行药理学阻断，与野生型小鼠相比，在BAL中的细胞模式和免疫球蛋白水平均未发现显著变化。我们的研究结果表明，通过应用激动剂THC激活ECS参与I型过敏的发展。然而，在观察到的结果中，CB 1/CB 2受体非依赖性信号传导似乎是可能的。(C)2010年Elsevier GmbH。All rights reserved.
The endocannabinoid system (ECS) consists of two cannabinoid (CB) receptors, namely CB1 and CB2 receptor, and their endogenous (endocannabinoids) and exogenous (cannabinoids, e.g. delta-9-tetrahydrocannabinol (THC)) ligands which bind to these receptors. Based on studies suggesting a role of THC and the ECS in inflammation, the objective of this study was to examine their involvement in type I hypersensitivity using a murine model of allergic airway inflammation. THC treatment of C57BL/6 wildtype mice dramatically reduced airway inflammation as determined by significantly reduced total cell counts in bronchoalveolar lavage (BAL). These effects were greatest when mice were treated during both, the sensitization and the challenge phase. Furthermore, systemic immune responses were significantly suppressed in mice which received THC during sensitization phase. To investigate a role of CB1/2 receptors in this setting, we used pharmacological blockade of CBI and/or CB2 receptors by the selective antagonists and moreover CB1/CB2 receptor double-knockout mice (CB1-/-/CB2-/-) and found neither significant changes in the cell patterns in BAL nor in immunoglobulin levels as compared to wildtype mice. Our results indicate that the activation of the ECS by applying the agonist THC is involved in the development of type I allergies. However, CB1/CB2 receptor-independent signalling seems likely in the observed results. (C) 2010 Elsevier GmbH. All rights reserved.