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Reactive oxygen species play a role in P2X7 receptor-mediated IL-6 production in spinal astrocytes
Journal article   Open access   Peer reviewed

Reactive oxygen species play a role in P2X7 receptor-mediated IL-6 production in spinal astrocytes

Frances M Munoz, Priya A Patel, Xinghua Gao, Yixiao Mei, Jingsheng Xia, Sofia Gilels and Huijuan Hu
Purinergic signalling, v 16(1)
Mar 2020
DOI: https://doi.org/10.1007/s11302-020-09691-5
PMID: 32146607
Featured in Collection :   UN Sustainable Development Goals @ Drexel
url
https://doi.org/10.1007/s11302-020-09691-5View
Published, Version of Record (VoR)Open Access (License Unspecified),  Open

Abstract

Animals Astrocytes - metabolism Interleukin-6 - biosynthesis Mice Reactive Oxygen Species - metabolism Receptors, Purinergic P2X7 - metabolism Signal Transduction - physiology Spinal Cord - metabolism
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.

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Domestic collaboration
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Web of Science research areas
Biochemistry & Molecular Biology
Neurosciences
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