Journal article
IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension
Hypertension (Dallas, Tex. 1979), Vol.78(5), pp.1450-1462
11/2021
DOI: 10.1161/HYPERTENSIONAHA.121.18219
PMCID: PMC8516065
PMID: 34628936
Abstract
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 necrosis factor-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.
Details
- Title: Subtitle
- IL (Interleukin)-17A Acts in the Brain to Drive Neuroinflammation, Sympathetic Activation, and Hypertension
- Creators
- Yiling Cao - Department of Internal Medicine (Y.C., Y.Y., S.-G.W.), University of Iowa Carver College of MedicineYang Yu - Department of Internal Medicine (Y.C., Y.Y., S.-G.W.), University of Iowa Carver College of MedicineBaojian Xue - Psychological and Brain Sciences (B.X., T.G.B., A.K.J.), University of Iowa Carver College of MedicineYe Wang - Department of Cardiology, the First Affiliated Hospital of Shandong First Medical University, China (Y.W.)Xiaolei Chen - Department of Nephrology, West China Hospital, Sichuan University, Chengdu, China (X.C.)Terry G Beltz - Psychological and Brain Sciences (B.X., T.G.B., A.K.J.), University of Iowa Carver College of MedicineAlan Kim Johnson - Iowa Neuroscience Institute (A.K.J., S.-G.W.), University of Iowa Carver College of MedicineShun-Guang Wei - Department of Cardiology, the First Affiliated Hospital of Shandong First Medical University, China (Y.W.)
- Resource Type
- Journal article
- Publication Details
- Hypertension (Dallas, Tex. 1979), Vol.78(5), pp.1450-1462
- DOI
- 10.1161/HYPERTENSIONAHA.121.18219
- PMID
- 34628936
- PMCID
- PMC8516065
- NLM abbreviation
- Hypertension
- ISSN
- 0194-911X
- eISSN
- 1524-4563
- Grant note
- R01 HL139521 / NHLBI NIH HHS R01 HL139575 / NHLBI NIH HHS R01 HL155091 / NHLBI NIH HHS
- Language
- English
- Date published
- 11/2021
- Academic Unit
- Psychological and Brain Sciences; Iowa Neuroscience Institute; Cardiovascular Medicine; Neuroscience and Pharmacology; Neurology (Pediatrics); Health, Sport, and Human Physiology ; Internal Medicine
- Record Identifier
- 9984213410502771
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