The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro
The function of microglia, either neuroprotection or neurotoxicity, is determined by the equilibrium among factors released from activated microglia in vitro
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DOI：
10.1016/j.brainres.2007.04.066
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发表时间：
2007-07-23
期刊：
影响因子：
2.9
通讯作者：
He, Bei Ping
中科院分区：
文献类型：
--
作者：
Li, Lu;Lu, Jia;He, Bei Ping
活化的小胶质细胞的相反功能，即神经保护或神经营养与神经破坏或神经毒性，已经在许多神经创伤和神经退行性疾病的实验模型中观察到。然而，在一组给定的条件下，参与确定激活的小胶质细胞执行哪种功能的机制仍有待阐明。我们目前的体外研究表明，神经保护性/神经营养性或神经破坏性/神经毒性小胶质细胞功能可以通过释放到微环境中的各种小胶质细胞因子之间的平衡来配置。当用较低浓度的脂多糖刺激的BV-2小胶质细胞条件培养基（LPS-BVCM）处理NSC-34神经元时，NSC-34神经元的活力增加，神经元突起的生长被促进，并且2，5-己二酮诱导的聚集体的形成被阻止。然而，当用更高浓度的相同LPS-BVCM处理NSC-34神经元时，神经元活力降低，诱导细胞凋亡，并阻止神经元突起的生长。对LPS-BVCM中细胞因子肿瘤坏死因子-α（TNF-α）、白细胞介素-1 β（IL-1 β）和IL-6的测量表明，每种细胞因子表达的上调在时间和数量上都有变化。据推测，LPS-BVCM浓度的改变可能会显著影响微环境中小胶质细胞因子的功能平衡，从而产生不同的小胶质细胞功能。(C)2007 Elsevier B. V.保留所有权利。
Opposing functions of activated microglia, namely neuroprotection or neurotrophy versus neurodestruction or neurotoxicity, have been observed in a number of experimental models of neurotrauma and neurodegenerative diseases. However, the mechanism(s) involved in the determination of which function activated microglia execute under a given set of conditions still remains to be elucidated. Our current in vitro study has revealed that a neuroprotective/neurotrophic or a neurodestructive/neurotoxic microglial function may be configured by the equilibrium among various microglial factors released into the microenvironment. When NSC-34 neurons were treated with lower concentrations of lipopolysaccharide-stimulated BV-2 microglial conditioned medium (LPS-BVCM), viability of the NSC-34 neurons increased, outgrowth of neuronal processes was promoted, and the formation of 2,5-hexanedione-induced aggregates was prevented. However, when NSC-34 neurons were treated with higher concentrations of the same LPS-BVCM, neuronal viability was reduced, apoptosis was induced and outgrowth of neuronal processes was prevented. Measurement of the cytokines tumor necrotic factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta), and IL-6 in the LPS-BVCM has shown that the upregulation in expression for each cytokine varied both temporally and quantitatively. It is postulated that an alteration in the concentration of the LPS-BVCM might significantly affect the functional balance of microglial factors in the microenvironment with a resultant different microglial function. (C) 2007 Elsevier B.V. All rights reserved.