MG53 attenuates lipopolysaccharide-induced neurotoxicity and neuroinflammation via inhibiting TLR4/NF-κB pathway in vitro and in vivo
MG53 attenuates lipopolysaccharide-induced neurotoxicity and neuroinflammation via inhibiting TLR4/NF-κB pathway in vitro and in vivo
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MG53 通过在体外和体内抑制 TLR4/NF-κ B 通路来减轻脂多糖诱导的神经毒性和神经炎症
DOI：
10.1016/j.pnpbp.2019.109684
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发表时间：
2019-12-20
影响因子：
5.6
通讯作者：
Ma, Shanshan
中科院分区：
文献类型：
--
作者：
Guan, Fangxia;Zhou, Xinkui;Ma, Shanshan
神经炎症在神经退行性疾病的发病和发展中起重要作用。脂多糖（Lipopolysaccharide，LPS）可诱导神经炎症，引起神经毒性，导致不同细胞和动物的细胞损伤或记忆障碍。在本研究中，我们研究了MG 53，TRIM家族蛋白质的成员，对LPS诱导的神经炎症和神经毒性在体外和体内的神经保护作用。MG 53通过抑制TNF-α、IL-6和IL-1 β的表达，显著保护HT 22细胞免受LPS诱导的细胞凋亡和细胞周期阻滞。此外，MG 53改善LPS诱导的小鼠记忆障碍和神经元细胞死亡。有趣的是，MG 53显著促进新生细胞存活，改善神经发生，并减轻神经炎症，这由LPS处理小鼠海马中IL-1 β和IL-6的产生较低、小胶质细胞活化较少证明。进一步的研究表明，MG 53在LPS处理的HT 22细胞和小鼠中显著抑制TLR 4表达和核因子-κ B（NF-κ B）磷酸化。总之，我们的研究结果表明，MG 53减轻LPS诱导的神经毒性和神经炎症部分通过抑制TLR 4/NF-κ B通路在体外和体内。
Neuroinflammation plays important roles in the pathogenesis and development of neurodegenerative disorders. Lipopolysaccharide (LPS) induces neuroinflammation and causes neurotoxicity, which results in cell damage or memory impairment in different cells and animals. In the present study, we investigated the neuroprotective effects of MG53, a member of the TRIM family proteins, against LPS-induced neuroinflammation and neurotoxicity in vitro and in vivo. MG53 significantly protected HT22 cells against LPS-induced cell apoptosis and cell cycle arrest by inhibiting TNF-alpha, IL-6 and IL-1 beta expression. In addition, MG53 ameliorated LPS-induced memory impairment and neuronal cell death in mice. Interestingly, MG53 significantly promoted newborn cell survival, improved neurogenesis, and mitigated neuroinflammation evidenced by lower production of IL-1 beta and IL-6, less activation of microglia in the hippocampus of LPS treated mice. Further studies demonstrated that MG53 significantly inhibited TLR4 expression and nuclear factor-kappa B (NF-kappa B) phosphorylation in LPS treated HT22 cells and mice. Taken together, our results suggested that MG53 attenuated LPS-induced neurotoxicity and neuroinflammation partly by inhibiting TLR4/NF-kappa B pathway in vitro and in vivo.