Upregulation of Chemokines in the Paraventricular Nucleus of the Hypothalamus in Rats with Stress-Induced Hypertension

Abstract

Background The neuroinflammation of paraventricular nucleus (PVN) of the hypothalamus has been implicated in the development of hypertension. The promoted invasion of peripheral immune cells into PVN may be attributed to the upregulation of chemokines, then exacerbating neuroinflammation. We studied the expressions of chemokines, activation of microglial cells, and inflammatory mediators in PVN of rats with stress-induced hypertension (SIH). Material/Methods SIH was induced by electrical foot shock combined with noise for 2 h twice a day, at an interval of 4 h for 14 consecutive days. At the end of the 14th day, fresh PVN tissues were collected to measure the expressions of chemokines using the RayBiotech antibody array. Results We are the first to report that the expression of CXCL7 was extremely high in PVN of control rats, and was significantly lower in SIH rats. The expressions of CCL2 and CX3CL1 in PVN of SIH rats significantly exceeded those of control rats. The numbers of CX3CR1 (receptor of CX3CL1)-immunostained cells and oxycocin-42 (OX-42, marker of microglia)-positive cells increased in PVN of the SIH rats. The stress enhanced the protein expressions of proinflammatory cytokines IL-6 and IL-17 and reduced those of anti-inflammatory cytokines TGF-β and IL-10 in PVN. Conclusions In PVN of SIH rats, chronic stress induced neuroinflammation characterized by the activated microglia and upregulated proinflammatory cytokines. Expressions of chemokines CXCL7, CX3CL1, and CCL2 were altered. The causal link of chemokines to PVN neuroinflammation and hypertension remain to be determined.

Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism

“…Previously, we demonstrated that different types of acute exercise, such as swimming and treadmill running, increased the Il6 mRNA levels in the hypothalamus of mice ( 14 ) Similarly, stress protocols up-regulated Il6 mRNA expression in rat hypothalamus ( 38 , 51 ). In addition, a high capacity of hypothalamic microglial cells of mice to produce IL6 under several acute or chronic circumstances has been demonstrated ( 52 ).…”

Hypothalamic inflammation in metabolic disorders and aging

“…The PVN in the hypothalamus is a crucial BP regulation center [205], controlling other important nuclei and their circuits in the CNS, especially the rostroventrolateral medulla and nucleus tractus solitarius in the hindbrain, which is necessary for BP control [206][207][208]. Several studies have reported elevated proinflammatory cytokines expression in the PVN of animal hypertension models [209][210][211][212][213]. Further, the microinjection of inflammatory cytokines, such as TNF-α or IL-1β, into the PVN results in increased sympathetic outflow and increased afferent cardiac sympathetic reflex associated with an elevated BP [214].…”

Multifaceted Roles of Chemokine C-X-C Motif Ligand 7 in Inflammatory Diseases and Cancer

“…Leukocyte infiltration into the vessel wall is a key step in the development of hypertension. Alterations in CXCL7 can lead to a change in the inflammatory state in stress hypertension ( Wu et al, 2020 ). Neutrophils play an important role in the development of delayed cerebral vasospasm (DCV) after aneurysmal subarachnoid hemorrhage.…”