小胶质细胞
福克斯O1
神经炎症
下调和上调
炎症
细胞凋亡
信号转导
癌症研究
药理学
生物
化学
免疫学
细胞生物学
蛋白激酶B
生物化学
基因
作者
Weihua Tao,Guibo Zhang,Chengyuan Liu,Lide Jin,Xuehua Li,Shuaifeng Yang
出处
期刊:Redox biology
[Elsevier]
日期:2023-10-01
卷期号:66: 102863-102863
被引量:5
标识
DOI:10.1016/j.redox.2023.102863
摘要
Low-dose lipopolysaccharide (LPS) protects against early brain injury (EBI) after subarachnoid hemorrhage (SAH). However, the mechanism underlying the neuroprotective roles of low-dose LPS remain largely undefined.A SAH mice model was established and the pathological changes of brain were evaluated by wet-dry weight method, HE and Nissl staining, and blood-brain barrier (BBB) permeability assay. Cell apoptosis and inflammation were monitored by TUNEL, flow cytometry and ELISA assays. qRT-PCR, immunofluorescence and Western blot were used to detect the expression of microglial polarization-related or oxidative stress-associated markers. Bioinformatics analysis, luciferase and ChIP assays were employed to detect the direct association between FOXO1 and IL-10 promoter. The ubiquitination of FOXO1 in the in vitro SAH model was detected by co-IP.Low-dose LPS alleviated SAH-induced neurological dysfunction, brain edema, BBB disruption, damage in the hippocampus, neuronal apoptosis and inflammation via modulating microglial M1/M2 polarization by IL-10/IL-10R1 signaling. Mechanistic studies showed that FOXO1 acted as a transcriptional activator of IL-10. USP19 mediated the deubiquitination of FOXO1 to activate IL-10/IL-10R1 signaling, thereby regulating microglial M1/M2 polarization. Functional experiments revealed that low-dose LPS upregulated USP19 to modulate microglial M1/M2 polarization via FOXO1/IL-10/IL-10R1 signaling in SAH mice.Low-dose LPS protected against EBI after SAH by modulating microglial M1/M2 polarization via USP19/FOXO1/IL-10/IL-10R1 signaling.
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