The Dr. Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Br J Pharmacol. 2012 Apr;165(8):2512-28. doi: 10.1111/j.1476-5381.2011.01461.x.
Apart from their effects on mood and reward, cannabinoids exert beneficial actions such as neuroprotection and attenuation of inflammation. The immunosuppressive activity of cannabinoids has been well established. However, the underlying mechanisms are largely unknown. We previously showed that the psychoactive cannabinoid Δ(9) -tetrahydrocannabinol (THC) and the non-psychoactive cannabidiol (CBD) differ in their anti-inflammatory signalling pathways.
To characterize the transcriptional effects of CBD and THC, we treated BV-2 microglial cells with these compounds and performed comparative microarray analysis using the Illumina MouseRef-8 BeadChip platform. Ingenuity Pathway Analysis was performed to identify functional subsets of genes and networks regulated by CBD and/or THC.
Overall, CBD altered the expression of many more genes; from the 1298 transcripts found to be differentially regulated by the treatments, 680 gene probe sets were up-regulated by CBD and 58 by THC, and 524 gene products were down-regulated by CBD and only 36 by THC. CBD-specific gene expression profile showed changes associated with oxidative stress and glutathione depletion, normally occurring under nutrient limiting conditions or proteasome inhibition and involving the GCN2/eIF2α/p8/ATF4/CHOP-TRIB3 pathway. Furthermore, CBD-stimulated genes were shown to be controlled by nuclear factors known to be involved in the regulation of stress response and inflammation, mainly via the (EpRE/ARE)-Nrf2/ATF4 system and the Nrf2/Hmox1 axis.
These observations indicated that CBD, but much less than THC, induced a cellular stress response in microglial cells and suggested that this effect could underlie its anti-inflammatory activity.
This article is part of a themed section on Cannabinoids in Biology and Medicine. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.165.issue-8. To view Part I of Cannabinoids in Biology and Medicine visit http://dx.doi.org/10.1111/bph.2011.163.issue-7.
除了对情绪和奖励的影响外，大麻素还具有神经保护和减轻炎症等有益作用。大麻素的免疫抑制活性已得到充分证实。然而，其潜在机制在很大程度上尚不清楚。我们之前曾表明，精神活性大麻素 Δ(9)-四氢大麻酚（THC）和非精神活性大麻二酚（CBD）在其抗炎信号通路中存在差异。
为了描述 CBD 和 THC 的转录效应，我们用这些化合物处理 BV-2 小胶质细胞，并使用 Illumina MouseRef-8 BeadChip 平台进行比较微阵列分析。进行了 Ingenuity 通路分析，以鉴定受 CBD 和/或 THC 调节的功能基因子集和网络。
总体而言，CBD 改变了更多基因的表达；在 1298 个被处理差异调控的转录本中，有 680 个基因探针集被 CBD 上调，58 个被 THC 上调，524 个基因产物被 CBD 下调，只有 36 个被 THC 下调。CBD 特异性基因表达谱显示与氧化应激和谷胱甘肽耗竭相关的变化，这些变化通常发生在营养限制条件下或蛋白酶体抑制下，涉及 GCN2/eIF2α/p8/ATF4/CHOP-TRIB3 途径。此外，研究表明，CBD 刺激的基因受到已知参与应激反应和炎症调节的核因子的控制，主要通过（EpRE/ARE）-Nrf2/ATF4 系统和 Nrf2/Hmox1 轴。
这些观察结果表明，CBD 诱导小胶质细胞发生细胞应激反应，但其程度远低于 THC，并表明这种作用可能是其抗炎活性的基础。
本文是关于大麻素在生物学和医学中的主题部分的一部分。要查看该部分中的其他文章，请访问 http://dx.doi.org/10.1111/bph.2012.165.issue-8。要查看大麻素在生物学和医学中的第 I 部分，请访问 http://dx.doi.org/10.1111/bph.2011.163.issue-7。
