1. IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation.
- Author
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Cao K, Liao X, Lu J, Yao S, Wu F, Zhu X, Shi D, Wen S, Liu L, and Zhou H
- Subjects
- Animals, Animals, Newborn, Cells, Cultured, Encephalitis chemically induced, Encephalitis immunology, Endothelial Cells immunology, Immunity, Innate physiology, Injections, Intraventricular, Interleukin-1 Receptor-Like 1 Protein immunology, Interleukin-33 immunology, Lipopolysaccharides toxicity, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Microglia immunology, Neutrophil Infiltration physiology, Encephalitis metabolism, Endothelial Cells metabolism, Interleukin-1 Receptor-Like 1 Protein biosynthesis, Interleukin-33 biosynthesis, Microglia metabolism
- 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. The role of IL-33/ST2 in LPS induced neuroinflammation.- Published
- 2018
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