Astrocytes mediate a remarkable variety of cellular functions, including gliotransmitter release. Under pathological conditions, high concentrations of the purinergic receptor agonist adenosine triphosphate (ATP) are released into the extracellular space leading to the activation of the purinergic P2X7 receptor, which in turn can initiate signaling cascades. It is well-established that reactive oxygen species (ROS) increase in macrophages and microglia following P2X7 receptor activation. However, direct evidence that activation of P2X7 receptor leads to ROS production in astrocytes is lacking to date. While it is known that P2X7R activation induces cytokine production, the mechanism involved in this process is unclear. In the present study, we demonstrated that P2X7 receptor activation induced ROS production in spinal astrocytes in a concentration-dependent manner. We also found that P2X7R-mediated ROS production is at least partially through NADPH oxidase. In addition, our ELISA data show that P2X7R-induced IL-6 release was dependent on NADPH oxidase-mediated production of ROS. Collectively, these results reveal that activation of the P2X7 receptor on spinal astrocytes increases ROS production through NADPH oxidase, subsequently leading to IL-6 release. Our results reveal a role of ROS in the P2X7 signaling pathway in mouse spinal cord astrocytes and may indicate a potential mechanism for the astrocytic P2X7 receptor in chronic pain.

中文翻译：

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活性氧在脊髓星形胶质细胞中P2X7受体介导的IL-6产生中起作用。

星形胶质细胞介导多种细胞功能，包括神经胶质递质的释放。在病理条件下，高浓度的嘌呤能受体激动剂三磷酸腺苷（ATP）释放到细胞外空间，导致嘌呤能P2X7受体活化，进而激活信号级联反应。众所周知，激活P2X7受体后，巨噬细胞和小胶质细胞中的活性氧（ROS）会增加。但是，迄今为止尚缺乏直接证据表明P2X7受体的激活会导致星形胶质细胞产生ROS。虽然已知P2X7R激活会诱导细胞因子的产生，但该过程涉及的机制尚不清楚。在目前的研究中，我们证明P2X7受体激活以浓度依赖的方式诱导脊髓星形胶质细胞中ROS的产生。我们还发现P2X7R介导的ROS产生至少部分通过NADPH氧化酶产生。此外，我们的ELISA数据表明P2X7R诱导的IL-6释放依赖于NADPH氧化酶介导的ROS产生。总的来说，这些结果表明脊髓星形胶质细胞上P2X7受体的激活通过NADPH氧化酶增加了ROS的产生，随后导致IL-6的释放。我们的研究结果揭示了ROS在小鼠脊髓星形胶质细胞的P2X7信号通路中的作用，并可能表明慢性疼痛中星形细胞P2X7受体的潜在机制。我们的ELISA数据表明P2X7R诱导的IL-6释放取决于NADPH氧化酶介导的ROS的产生。总的来说，这些结果表明脊髓星形胶质细胞上P2X7受体的激活通过NADPH氧化酶增加了ROS的产生，随后导致IL-6的释放。我们的研究结果揭示了ROS在小鼠脊髓星形胶质细胞的P2X7信号通路中的作用，并可能表明慢性疼痛中星形细胞P2X7受体的潜在机制。我们的ELISA数据表明P2X7R诱导的IL-6释放取决于NADPH氧化酶介导的ROS的产生。总的来说，这些结果表明脊髓星形胶质细胞上P2X7受体的激活通过NADPH氧化酶增加了ROS的产生，随后导致IL-6的释放。我们的研究结果揭示了ROS在小鼠脊髓星形胶质细胞的P2X7信号通路中的作用，并可能表明慢性疼痛中星形细胞P2X7受体的潜在机制。