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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation

Authors: Kelei Cao, Xiang Liao, Jiahui Lu, Shu Yao, Fengjiao Wu, Xingxing Zhu, Dongyan Shi, Shuang Wen, Lixin Liu, Hong Zhou

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Interleukin-33 (IL-33) is increasingly being recognized as a key immunomodulatory cytokine in many neurological diseases.

Methods

In the present study, wild-type (WT) and IL-33−/− mice received intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS) to induce neuroinflammation. Intravital microscopy was employed to examine leukocyte–endothelial interactions in the brain vasculature. The degree of neutrophil infiltration was determined by myeloperoxidase (MPO) staining. Real-time PCR and western blotting were used to detect endothelial activation. Enzyme-linked immunosorbent assay and quantitative PCR were conducted to detect pro-inflammatory cytokine levels in the brain.

Results

In IL-33−/− mice, neutrophil infiltration in the brain cortex and leukocyte–endothelial cell interactions in the cerebral microvessels were significantly decreased as compared to WT mice after LPS injection. In addition, IL-33−/− mice showed reduced activation of microglia and cerebral endothelial cells. In vitro results indicated that IL-33 directly activated cerebral endothelial cells and promoted pro-inflammatory cytokine production in LPS-stimulated microglia.

Conclusions

Our study indicated that IL-33/ST2 signaling plays an important role in the activation of microglia and cerebral endothelial cells and, therefore, is essential in leukocyte recruitment in brain inflammation.

Graphical abstract

The role of IL-33/ST2 in LPS induced neuroinflammation
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Metadata
Title
IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation
Authors
Kelei Cao
Xiang Liao
Jiahui Lu
Shu Yao
Fengjiao Wu
Xingxing Zhu
Dongyan Shi
Shuang Wen
Lixin Liu
Hong Zhou
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1169-6

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