IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension.
IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension.
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IL(白介素17A)在大脑中起作用，推动神经炎症、交感神经激活和高血压。
DOI：
10.1161/hypertensionaha.121.18219
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发表时间：
2021-11
期刊：
影响因子：
--
通讯作者：
Wei SG
中科院分区：
文献类型：
--
作者：
Cao Y;Yu Y;Xue B;Wang Y;Chen X;Beltz TG;Johnson AK;Wei SG
白细胞介素(IL)-17A是促进慢性组织炎症的关键炎症介质。本研究旨在确定IL-17A是否在正常和高血压动物的神经炎症、血流动力学和交感神经流出中发挥作用。在脲烷麻醉大鼠中，静脉注射IL-17A可引起血压（BP）、心率（HR）和肾交感神经活动（RSNA）的持续升高，而下丘脑室旁核（PVN）中的IL-17受体A (IL-17RA) siRNA可显著减弱这些升高。脑室（ICV）或PVN内微量注射IL-17A也能引起类似的BP、HR和RSNA的兴奋反应。IV IL-17A上调PVN中IL-17A、IL-17F和IL-17RA的mRNA水平。此外，IV IL-17A激活脑内胶质细胞，升高PVN中炎症细胞因子和趋化因子的基因表达，PVN显微注射IL-17RA siRNA可显著降低这些基因表达。用小胶质细胞或星形胶质细胞抑制剂预处理可减弱PVN IL-17A对BP、HR和RSNA的反应。此外，ICV IL-17A在PVN中激活了转化生长因子-β活化激酶1、p44/42丝裂原活化蛋白激酶和转录核因子κB。IL-17A与TNF-α或IL-1β协同作用，夸大其对血流动力学和交感反应的影响。中央干预抑制PVN中IL-17RA可显著降低血管紧张素ii诱导的高血压、神经炎症和交感神经张力。总的来说，这些数据表明，大脑中的IL-17A促进神经炎症，促进交感神经激活和高血压，可能是通过与大脑内各种炎症介质相互作用的协同机制。
Interleukin (IL)-17A is a key inflammatory mediator contributing to chronic tissue inflammation. The present study sought to determine whether IL-17A plays a role in regulating neuroinflammation, hemodynamics and sympathetic outflow in normal and hypertensive animals. In urethane-anesthetized rats, intravenous (IV) injection of IL-17A induced dramatic and prolonged increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA), which were significantly attenuated by an IL-17 receptor A (IL-17RA) siRNA in the hypothalamic paraventricular nucleus (PVN). Either intracerebroventricular (ICV) or PVN microinjection of IL-17A also elicited a similar excitatory response in BP, HR and RSNA. IV IL-17A upregulated the mRNA level of IL-17A, IL-17F and IL-17RA in the PVN. Additionally, IV IL-17A activated brain-resident glial cells and elevated the gene expression of inflammatory cytokines and chemokines in the PVN, which were markedly diminished by PVN microinjection of IL-17RA siRNA. Pretreatments with microglia or astrocyte inhibitor attenuated the increase in BP, HR and RSNA in response to PVN IL-17A. Moreover, ICV IL-17A activated transforming growth factor-β activated kinase 1, p44/42 mitogen-activated protein kinase and transcriptional nuclear factor κB in the PVN. IL-17A interacted with TNF-α or IL-1β synergistically to exaggerate its influence on hemodynamic and sympathetic responses. Central intervention suppressing IL-17RA in the PVN significantly reduced angiotensin II-induced hypertension, neuroinflammation and sympathetic tone in the rats. Collectively, these data indicated that IL-17A in the brain promotes neuroinflammation to advance sympathetic activation and hypertension, probably by a synergistic mechanism involving the interaction with various inflammatory mediators within the brain.