Division of Basic Medical Sciences, St George's, University of London, London, UK.
J Neuroimmunol. 2009 Nov 30;216(1-2):118-21. doi: 10.1016/j.jneuroim.2009.07.008. Epub 2009 Aug 15.
Activated microglial cells generate reactive oxygen species (ROS), which have detrimental effects in neuroinflammatory and neurodegenerative diseases. In the present study, we have identified a novel mechanism involved in microglial NADPH oxidase-mediated ROS production. In PMA-stimulated microglia, ROS production was substantially reduced upon inhibition of the non-selective cation channel TRPV1 with La(3+), ruthenium red, capsazepine and 5-iodo-resinferatoxin. Furthermore, sustained membrane depolarization, a hallmark of NADPH oxidase activity in phagocytes, was found to induce non-selective cation/TRPV1 channel activity in microglia. Together, our data suggest that TRPV1 channels are involved in regulating NADPH oxidase-mediated ROS generation in microglia.
激活的小胶质细胞会产生活性氧（ROS），在神经炎症和神经退行性疾病中具有有害作用。在本研究中，我们已经确定了一个新的机制，涉及小胶质细胞 NADPH 氧化酶介导的 ROS 产生。在 PMA 刺激的小胶质细胞中，用 La(3+)、钌红、辣椒素和 5-碘树脂毒素抑制非选择性阳离子通道 TRPV1 后，ROS 的产生明显减少。此外，持续的膜去极化，吞噬细胞 NADPH 氧化酶活性的标志，被发现会诱导小胶质细胞中非选择性阳离子/ TRPV1 通道的活性。综上所述，我们的数据表明 TRPV1 通道参与调节小胶质细胞中 NADPH 氧化酶介导的 ROS 生成。
