HMGB1 A box protects neurons by potently inhibiting both microglia and T cell-mediated inflammation in a mouse Parkinson's disease model
HMGB1 A box protects neurons by potently inhibiting both microglia and T cell-mediated inflammation in a mouse Parkinson's disease model
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HMGB1 A 盒通过有效抑制小鼠帕金森病模型中小胶质细胞和 T 细胞介导的炎症来保护神经元
DOI：
10.1042/cs20200553
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发表时间：
2020
期刊：
影响因子：
6
通讯作者：
Zhaoliang Su
中科院分区：
文献类型：
--
作者：
Yu Tian;Yuwen Cao;Rong Chen;Yufeng Jing;Lin Xia;Shiqing Zhang;Huaxi Xu;Zhaoliang Su
In the subacute Parkinson’s disease (PD) mice model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), injection of HMGB1 competitive inhibitor protein HMGB1 A box and the ethyl pyruvate (EP) that inhibit the release of HMGB1 from cells restored the number of dopaminergic neurons and TH+fibers in the SN and striatum. Our data show that A box up-regulated CD200-CD200R signal of microglia inhibited the activation of microglia mediated by HMGB1, and the production of TNF-α, IL-1β and IL-6in vivoandin vitromixed culture system. Microglia overexpressing CD200R produced less inflammatory chemokines and reduced the loss of TH+neurons. In addition, HMGB1 A box decreased the level of CCL5 and significantly inhibited the infiltration of almost all T cells including Th17 and the proportion of Th17 in CD4+T cells.In vitroMPP+induced model and HMGB1-stimulated mesencephalic cell system activated microglia induced the differentiation of naïve T cells to Th17, and A box significantly inhibited this process. To sum up, our results show that HMGB1 A box targeting HMGB1, which effectively reduces the activation of microglia in MPTP PD model by restoring CD200-CD200R signal inhibit microglia mediated neuroinflammation and the differentiation of T cells to Th17.
