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

IL-33/ST2 plays a critical role in endothelial cell activation and microglia-mediated neuroinflammation modulation.
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IL-33/ST2在内皮细胞激活和小胶质细胞介导的神经炎症调节中发挥关键作用

DOI:
10.1186/s12974-018-1169-6
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发表时间:
2018-05-04
影响因子:
9.3
通讯作者:
Zhou H
Zhou H
中科院分区:
医学1区
文献类型:
--
作者:
Cao K;Liao X;Lu J;Yao S;Wu F;Zhu X;Shi D;Wen S;Liu L;Zhou H

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白细胞介素-33(IL-33)在许多神经系统疾病中被认为是一种重要的免疫调节细胞因子。在本研究中,野生型(WT)和IL-33−/−小鼠接受脑室内(i. c. v.)注射脂多糖(LPS)诱导神经炎症。采用活体显微镜检查脑血管系统中白细胞-内皮细胞的相互作用。髓过氧化物酶(MPO)染色测定中性粒细胞浸润程度。实时荧光定量PCR和免疫印迹法检测内皮细胞活化情况。采用酶联免疫吸附试验和定量PCR检测脑组织中促炎细胞因子水平。在IL-33−/−小鼠中,与WT小鼠相比,LPS注射后,脑皮质中的中性粒细胞浸润和脑微血管中的白细胞-内皮细胞相互作用显著减少。此外,IL-33−/−小鼠表现出小胶质细胞和脑内皮细胞的活化减少。体外实验结果表明,IL-33直接激活脑内皮细胞,并促进LPS刺激的小胶质细胞中促炎细胞因子的产生。我们的研究表明,IL-33/ST 2信号在小胶质细胞和脑内皮细胞的活化中起着重要作用,因此,在脑炎症中白细胞募集中是必不可少的。IL-33/ST 2在LPS诱导的神经炎症中的作用
Interleukin-33 (IL-33) is increasingly being recognized as a key immunomodulatory cytokine in many neurological diseases. 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. 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. 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
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