Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia.
Studies of involvement of G-protein coupled receptor-3 in cannabidiol effects on inflammatory responses of mouse primary astrocytes and microglia.
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DOI：
10.1371/journal.pone.0251677
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Shao H
中科院分区：
文献类型：
--
作者：
Wu J;Chen N;Liu Y;Godlewski G;Kaplan HJ;Shrader SH;Song ZH;Shao H
大麻二酚（CBD）具有抗炎和神经保护特性，并且被认为在中枢神经系统（CNS）疾病的临床前和临床治疗中是有效的。两种主要类型的CNS胶质细胞，星形胶质细胞和小胶质细胞，在CNS疾病的发展和发病机制中起关键作用。然而，CBD对这些神经胶质细胞发挥抗炎和神经保护作用的机制尚未完全阐明。在本研究中，我们检测了CBD对小鼠原代星形胶质细胞和小胶质细胞炎症反应的影响。我们还研究了CBD对细胞因子释放的影响是否由G蛋白偶联受体3（GPR 3）介导，GPR 3最近被鉴定为CBD的新型受体。我们的结果表明，CBD在体外和体内均能抑制Toll样受体4（TLR 4）配体脂多糖（LPS）刺激的星形胶质细胞和小胶质细胞的炎症反应。此外，CBD降低了LPS刺激的星形胶质细胞中STAT 3和NF-κB信号通路的磷酸化。然而，在两种类型的胶质细胞中，CBD对促炎性细胞因子产生的抑制作用与GPR 3表达无关。因此，尽管CBD在改善星形胶质细胞和小胶质细胞的活化方面是有效的，但其作用机制仍需要进一步研究。我们的数据支持CBD可能对涉及神经炎症的神经系统疾病具有治疗潜力的概念。
Cannabidiol (CBD) exhibits anti-inflammatory and neuroprotective properties and is suggested to be effective in the pre-clinical and clinical treatment of illnesses of the central nervous system (CNS). Two major types of CNS glial cells, astrocytes and microglia, play critical roles in the development and pathogenesis of CNS diseases. However, the mechanisms by which CBD plays an anti-inflammatory and neuroprotective role for these glial cells have not been fully elucidated. In this study, we examined the effects of CBD on the inflammatory response of mouse primary astrocytes and microglia. We also investigated whether the effect of CBD on cytokine release is mediated by the G protein coupled receptor 3 (GPR3), which was recently identified as a novel receptor for CBD. Our results showed that CBD inhibited inflammatory responses of astrocytes and microglia stimulated with lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR4) ligand in vitro and in vivo. In addition, CBD reduced the phosphorylation of STAT3 and NF-κB signaling pathways in LPS-stimulated astrocytes. However, the inhibitory effect of CBD on pro-inflammatory cytokine production was independent of GPR3 expression in both types of glial cells. Thus, although CBD is effective in ameliorating the activation of astrocytes and microglia, its mechanism of action still requires further study. Our data support the concept that CBD may have therapeutic potential for neurological disorders that involve neuroinflammation.
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