Dataset Information

?-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

ABSTRACT: BACKGROUND:Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS. METHODS:Splenic ARRB2 expression and the sympathetic system activity were detected after establishing transient models of middle cerebral artery occlusion (MCAO). In addition, a correlation between ARRB2 expression and the sympathetic system activity was analyzed using a linear correlation analysis. Any SIDS reflected in monocyte dysfunction was investigated by measuring inflammatory cytokine secretion and neurological deficit scores and infarct volume were tested to assess neurological outcome. Further, ARRB2 expression in the monocytes was knocked down in vitro by siRNAs. Following the stimulation of noradrenaline and lipopolysaccharide, cytokine secretion and the nuclear factor-?B (NF-?B) pathway were evaluated to gain insight into the mechanisms related to the contribution of ARRB2 to adrenergic-induced monocyte dysfunction. RESULTS:Splenic ARRB2 expression was significantly increased after stroke and also showed a significant positive correlation with the sympathetic system activity. Stroke-induced monocyte dysfunction resulted in an increase of the interleukin-10 (IL-10) level as well as a decrease of the interleukin-6 (IL-6), tumor necrosis factor-? (TNF-?) and interleukin-1? (IL-1?) levels. Also, blockade of adrenergic-activity significantly reversed these cytokine levels, and blockade of adrenergic-activity improved stroke-induced neurological results. However, the improved neurological results had no significant correlation with ARRB2 expression. Furthermore, the in vitro results showed that the deficiency of ARRB2 dramatically repealed adrenergic-induced monocyte dysfunction and the inhibition of NF-?B signaling phosphorylation activity. CONCLUSIONS:ARRB2 is implicated in the sympathetic-triggered SIDS, in particular, monocyte dysfunction after stroke. Accordingly, ARRB2 may be a promising therapeutic target for the immunological management of stroke in a clinic.

SUBMITTER: Wang H

PROVIDER: S-EPMC5894164 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

β-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

Wang Huan H Deng Qi-Wen QW Peng Ai-Ni AN Xing Fang-Lan FL Zuo Lei L Li Shuo S Gu Zheng-Tian ZT Yan Fu-Ling FL

Journal of neuroinflammation 20180410 1

<h4>Background</h4>Stroke-induced immunodeficiency syndrome (SIDS) is regarded as a protective mechanism for secondary inflammatory injury as well as a contributor to infection complications. Although stroke-induced hyperactivation of the sympathetic system is proved to facilitate SIDS, the involved endogenous factors and pathways are largely elusive. In this study, we aim to investigate the function of beta-arrestin-2 (ARRB2) in the sympathetic-mediated SIDS.<h4>Methods</h4>Splenic ARRB2 expres ...[more]

PMID: 29636059

Similar Datasets

Project description:BackgroundStroke-induced immunodepression is a well characterized complication of acute ischemic stroke. In experimental studies beta-blocker therapy reversed stroke-induced immunodepression, reduced infection rates and mortality. Recent, heterogeneous studies in stroke patients could not provide evidence of a protective effect of beta-blocker therapy. Aim of this study is to investigate the potential preventive effect of beta-blockers in subgroups of patients at high risk for stroke-induced immunodepression.MethodsData from a prospectively derived registry of major stroke patients receiving endovascular therapy between 2011-2017 in a tertiary stroke center (University Medical Center Göttingen. Germany) was used. The effect of beta-blocker therapy on pneumonia, urinary tract infection, sepsis and mortality was assessed using multivariate logistic regression analysis.ResultsThree hundred six patients with a mean age of 72 ± 13 years and a median NIHSS of 16 (IQR 10.75-20) were included. 158 patients (51.6%) had pre-stroke- and continued beta-blocker therapy. Beta-blocker therapy did not reduce the incidence of pneumonia (OR 0.78, 95% CI 0.31-1.92, p = 0.584), urinary tract infections (OR 1.51, 0.88-2.60, p = 0.135), sepsis (OR 0.57, 0.18-1.80, p = 0.334) or mortality (OR 0.59, 0.16-2.17, p = 0.429). Strokes involving the insula and anterio-medial cortex increased the risk for pneumonia (OR 4.55, 2.41-8.56, p<0.001) and sepsis (OR 4.13, 1.81-9.43, p = 0.001), while right hemispheric strokes increased the risk for pneumonia (OR 1.60, 0.92-2.77, p = 0.096). There was a non-significantly increased risk for urinary tract infections in patients with beta-blocker therapy and insula/anterio-medial cortex strokes (OR 3.12, 95% CI 0.88-11.05, p = 0.077) with no effect of beta-blocker therapy on pneumonia, sepsis or mortality in both subgroups.ConclusionsIn major ischemic stroke patients, beta-blocker therapy did not lower post-stroke infection rates and was associated with urinary tract infections in a subgroup with insula/anterio-medial strokes.

Dataset Information

?-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

Publications

β-arrestin2 functions as a key regulator in the sympathetic-triggered immunodepression after stroke.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets