Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses
Nerve Growth Factor modulates LPS - induced microglial glycolysis and inflammatory responses
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DOI：
10.1016/j.yexcr.2019.02.023
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发表时间：
2019-04-15
影响因子：
3.7
通讯作者：
Alexaki, Vasileia Ismini
中科院分区：
文献类型：
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作者：
Fodelianaki, Georgia;Lansing, Felix;Alexaki, Vasileia Ismini
小胶质细胞，中枢神经系统的实质免疫细胞，协调神经炎症反应感染或损伤，并促进组织修复。然而，异常的小神经胶质细胞反应是神经退行性疾病的组成部分，并严重促进疾病进展。因此，阐明小胶质细胞介导的神经炎症是如何受内源性因素调节的是很重要的。在这里，我们探讨了神经生长因子（NGF），丰富的神经营养因子，对小胶质细胞炎症反应的影响。NGF通过其高亲和力受体TrkA下调LPS诱导的小鼠原代小胶质细胞中促炎细胞因子和NO的产生，并抑制TLR 4介导的NF-κ B和JNK途径的活化。此外，如葡萄糖摄取减少和糖酵解酶Pfk β 3和Ldh α表达减少所示，NGF减弱了小胶质细胞中LPS增强的糖酵解活性。同样，2DG介导的糖酵解抑制强烈下调LPS诱导的小胶质细胞中细胞因子的产生。我们的研究结果表明，NGF减弱小胶质细胞的促炎症反应，从而可能有助于调节小胶质细胞介导的神经炎症。
Microglia, the parenchymal immune cells of the central nervous system, orchestrate neuroinflammation in response to infection or damage, and promote tissue repair. However, aberrant rnicroglial responses are integral to neurodegenerative diseases and critically contribute to disease progression. Thus, it is important to elucidate how microglia - mediated neuroinflammation is regulated by endogenous factors. Here, we explored the effect of Nerve Growth Factor (NGF), an abundant neurotrophin, on microglial inflammatory responses. NGF, via its high affinity receptor TrkA, downregulated LPS - induced production of pro-inflammatory cytokines and NO in primary mouse microglia and inhibited TLR4 - mediated activation of the NF-kappa B and JNK pathways. Furthermore, NGF attenuated the LPS - enhanced glycolytic activity in microglia, as suggested by reduced glucose uptake and decreased expression of the glycolytic enzymes Pfk beta 3 and Ldh alpha. Consistently, 2DG - mediated glycolysis inhibition strongly downregulated LPS - induced cytokine production in microglial cells. Our findings demonstrate that NGF attenuates pro-inflammatory responses in microglia and may thereby contribute to regulation of microglia - mediated neuroinflammation.