IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension

作者：Yiling Cao, Yang Yu, Baojian Xue, Ye Wang, Xiaolei Chen, Terry G. Beltz, Alan Kim Johnson, Shun‐Guang Wei · 发表于：Hypertension · 年份：2021 · DOI：10.1161/hypertensionaha.121.18219 · 被引用次数：31 · 研究领域：Psoriasis: Treatment and Pathogenesis、Tryptophan and brain disorders、Whipple's Disease and Interleukins

IL (Interleukin)-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 injection of IL-17A induced dramatic and prolonged increases in blood pressure, heart rate, and renal sympathetic nerve activity, which were significantly attenuated by an IL-17RA (IL-17 receptor A) siRNA in the hypothalamic paraventricular nucleus (PVN). Either intracerebroventricular or PVN microinjection of IL-17A also elicited a similar excitatory response in blood pressure, heart rate, and renal sympathetic nerve activity. Intravenous injection of IL-17A upregulated the mRNA level of IL-17A, IL-17F, and IL-17RA in the PVN. Additionally, intravenous injection of 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 inhibitors attenuated the increase in blood pressure, heart rate, and renal sympathetic nerve activity in response to PVN IL-17A. Moreover, intracerebroventricular injection of IL-17A activated TGF (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 tumor ne...