Blockade of IL-17AIL-17R Pathway Protected Mice from Sepsis-Associated Encephalopathy by Inhibition of Microglia Activation
Joint Authors
Tao, Tianzhu
Ye, Bo
Zhao, Andong
Wen, Liyuan
He, Xiaofei
Liu, Yi
Fu, Qiang
Mi, Weidong
Lou, Jingsheng
Source
Issue
Vol. 2019, Issue 2019 (31 Dec. 2019), pp.1-11, 11 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2019-10-07
Country of Publication
Egypt
No. of Pages
11
Main Subjects
Abstract EN
Sepsis-associated encephalopathy (SAE) is a poorly understood condition that leads to long-term cognitive impairment and increased mortality in survivors.
Recent research revealed that IL-17A/IL-17R might serve as a checkpoint in microglia-mediated neuroinflammation.
The present study was designed to determine the specific role of IL-17A-mediated microglia activation in the development of SAE.
A mouse model of SAE was induced by cecal ligation and puncture (CLP), and behavior performance was evaluated by the inhibitory avoidance test and the open field test.
Cytokine expression and microglia activation in brain tissue were determined at 6 h, 12 h, 24 h, 48 h, and day 7 post surgery.
Further, septic mice were intracerebral ventricle- (i.c.v.-) injected with recombinant IL-17A, anti-IL-17A ab, anti-IL-17R ab, or isotype controls to evaluate the potential effects of IL-17A/IL-17R blockade in the prevention of SAE.
Septic peritonitis induced significant impairment of learning memory and exploratory activity, which was associated with a higher expression of IL-17A, IL-1β, and TNF-α in the brain homogenate.
Fluorescence intensity of Iba-1 and IL-17R in the hippocampus was significantly increased following CLP.
Treatment with recombinant IL-17A enhanced the neuroinflammation and microglia activation in CLP mice.
On the contrary, neutralizing anti-IL-17A or anti-IL-17R antibodies mitigated the CNS inflammation and microglia activation, thus alleviating the cognitive dysfunction.
Furthermore, as compared to the sham control, microglia cultured from CLP mice produced significantly higher levels of cytokines and expressed with higher fluorescence intensity of Iba-1 in response to IL-17A or LPS.
Pretreatment with anti-IL-17R ab suppressed the Iba-1 expression and cytokine production in microglia stimulated by IL-17A.
In conclusion, blockade of the IL-17A/IL-17R pathway inhibited microglia activation and neuroinflammation, thereby partially reversing sepsis-induced cognitive impairment.
The present study suggested that the IL-17A/IL-17R signaling pathway had an important, nonredundant role in the development of SAE.
American Psychological Association (APA)
Ye, Bo& Tao, Tianzhu& Zhao, Andong& Wen, Liyuan& He, Xiaofei& Liu, Yi…[et al.]. 2019. Blockade of IL-17AIL-17R Pathway Protected Mice from Sepsis-Associated Encephalopathy by Inhibition of Microglia Activation. Mediators of Inflammation،Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1193489
Modern Language Association (MLA)
Ye, Bo…[et al.]. Blockade of IL-17AIL-17R Pathway Protected Mice from Sepsis-Associated Encephalopathy by Inhibition of Microglia Activation. Mediators of Inflammation No. 2019 (2019), pp.1-11.
https://search.emarefa.net/detail/BIM-1193489
American Medical Association (AMA)
Ye, Bo& Tao, Tianzhu& Zhao, Andong& Wen, Liyuan& He, Xiaofei& Liu, Yi…[et al.]. Blockade of IL-17AIL-17R Pathway Protected Mice from Sepsis-Associated Encephalopathy by Inhibition of Microglia Activation. Mediators of Inflammation. 2019. Vol. 2019, no. 2019, pp.1-11.
https://search.emarefa.net/detail/BIM-1193489
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1193489