To study the anti-inflammatory potential of the two synthetic cannabinoids 4′-F-CBD and HU-910, we used post-natal brain cultures of mouse microglial cells and astrocytes activated by reference inflammogens. We found that 4′-F-CBD and HU-910 efficiently curtailed the release of TNF-α, IL-6, and IL-1β in microglia and astrocytes activated by the bacterial Toll-Like Receptor (TLR)4 ligand LPS. Upon LPS challenge, 4′-F-CBD and HU-910 also prevented the activation of phenotypic activation markers specific to microglia and astrocytes, that is, Iba-1 and GFAP, respectively. In microglial cells, the two test compounds also efficiently restrained LPS-stimulated release of glutamate, a non-cytokine inflammation marker for these cells. The immunosuppressive effects of the two cannabinoid compounds were concentration-dependent and observable between 1 and 10 μM. These effects were not dependent on cannabinoid or cannabinoid-like receptors. Both 4′-F-CBD and HU-910 were also capable of restraining the inflammogenic activity of Pam3CSK4, a lipopeptide that activates TLR2, and of BzATP, a prototypic agonist of P2X7 purinergic receptors, suggesting that these two cannabinoids could exert immunosuppressive effects against a variety of inflammatory stimuli. Using LPS-stimulated microglia and astrocytes, we established that the immunosuppressive action of 4′-F-CBD and HU-910 resulted from the inhibition of ROS produced by NADPH oxidase and subsequent repression of NF-κB-dependent signaling events. Our results suggest that 4′-F-CBD and HU-910 may have therapeutic utility in pathological conditions where neuroinflammatory processes are prominent.

中文翻译：

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两种合成大麻素化合物4′-F-CBD和HU-910有效抑制脑小胶质细胞和星形胶质细胞的炎症反应

为了研究两种合成大麻素 4'-F-CBD 和 HU-910 的抗炎潜力，我们使用了由参考炎症原激活的小鼠小胶质细胞和星形胶质细胞的产后脑培养物。我们发现，4'-F-CBD 和 HU-910 有效地减少了细菌 Toll 样受体 (TLR)4 配体 LPS 激活的小胶质细胞和星形胶质细胞中 TNF-α、IL-6 和 IL-1β 的释放。LPS 攻击后，4'-F-CBD 和 HU-910 还分别阻止小胶质细胞和星形胶质细胞特异的表型激活标记物（即 Iba-1 和 GFAP）的激活。在小胶质细胞中，两种测试化合物还有效地抑制了 LPS 刺激的谷氨酸释放，谷氨酸是这些细胞的非细胞因子炎症标记物。两种大麻素化合物的免疫抑制作用具有浓度依赖性，并且在 1 至 10 μM 之间可观察到。这些作用不依赖于大麻素或大麻素样受体。4'-F-CBD 和 HU-910 还能够抑制 Pam3CSK4（一种激活 TLR2 的脂肽）和 BzATP（P2X7 嘌呤能受体的原型激动剂）的致炎活性，表明这两种大麻素可以对各种炎症刺激。使用 LPS 刺激的小胶质细胞和星形胶质细胞，我们确定 4'-F-CBD 和 HU-910 的免疫抑制作用是由于抑制 NADPH 氧化酶产生的 ROS 以及随后抑制 NF-κB 依赖性信号传导事件所致。我们的结果表明，4'-F-CBD 和 HU-910 可能对神经炎症过程突出的病理状况具有治疗作用。