神经炎症
TLR4型
小胶质细胞
组蛋白脱乙酰基酶
组蛋白脱乙酰基酶2
NF-κB
污渍
脂多糖
促炎细胞因子
炎症
NFKB1型
细胞生物学
信号转导
化学
癌症研究
生物
免疫学
组蛋白
生物化学
转录因子
基因
作者
Fangzhou Jiao,Yao Wang,Haiyue Zhang,Wenbin Zhang,Lu-Wen Wang,Zuojiong Gong
标识
DOI:10.1007/s11064-018-2532-9
摘要
Neuroinflammation involves in the progression of many central nervous system diseases. Several studies have shown that histone deacetylase (HDAC) inhibitors modulated inflammatory responses in lipopolysaccharide (LPS) stimulated microglia. While, the mechanism is still unclear. The aim of present study was to investigate the effect of HDAC2 inhibitor CAY10683 on inflammatory responses and TLR4/NF-κB signaling pathways in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. The effect of CAY10683 on cell viability of BV2 microglial cells was detected by CCK-8 assay. The expressions of inflammatory cytokines were analyzed by western blotting and RT-PCR respectively. The TLR4 protein expression was measured by western blotting, immunofluorescence, immunohistochemistry respectively. The protein expressions of MYD88, phospho-NF-κB p65, NF-κB-p65, acetyl-H3 (AH3), H3, and HDAC2 were analyzed by western blotting. We found that CAY10683 could inhibit expression levels of inflammatory cytokine TNF-α and IL-1β in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. It could induce TLR4, MYD88, phospho-NF-κB p65, and HDAC2 expressions. Moreover, CAY10683 increased the acetylation of histones H3 in LPS activated BV2 microglial cells and LPS induced mice neuroinflammation. Taken together, our findings suggested that HDAC2 inhibitor CAY10683 could suppress neuroinflammatory responses and TLR4/NF-κB signaling pathways by acetylation after LPS stimulation.
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