N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli
N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli
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由 LPS 和 IL4 极化的 N9 小胶质细胞对二次环境刺激表现出不同的反应。
DOI：
10.1016/j.cellimm.2012.06.001
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发表时间：
2012-07-01
影响因子：
4.3
通讯作者：
Han, Hua
中科院分区：
文献类型：
--
作者：
Liu, Hong-Cui;Zheng, Min-Hua;Han, Hua
小胶质细胞参与了中枢神经系统许多炎症相关的病理过程的调节，但小胶质细胞的激活是如何被调节的还没有完全了解。在这里，通过使用小胶质细胞系，我们表明，小胶质细胞，像其他巨噬细胞，被激活的炎症刺激的极化方式。LPS极化的M1小胶质细胞似乎不能响应于二次IL 4刺激，而IL 4极化的M2小胶质细胞可以响应于二次LPS刺激。我们还表明，Notch信号参与小胶质细胞极化。当阻断Notch信号时，M1极化被抑制，而M2极化被促进。Notch信号抑制剂的撤销不允许M2 N9细胞在LPS刺激后恢复到M1，这表明Notch阻断对小胶质细胞极化的影响可以被细胞“记忆”。这些结果表明，复杂的机制，包括在巨噬细胞极化的调节表观遗传程序。(C)2012 Elsevier Inc. All rights reserved.
Microglia participates in the regulation of many inflammation-related pathological processes in the central nervous system, but how microglial activation is regulated has not been fully understood. Here, by using a microglial cell line, we show that microglia, like other macrophages, are activated by inflammatory stimuli in a polarized manner. The LPS-polarized M1 microglia appeared to be unable to respond to a secondary IL4 stimulation, while IL4-polarized M2 microglia could respond to secondary LPS stimulation. We also show that Notch signaling is involved in microglial polarization. When Notch signaling was blocked, the M1 polarization was suppressed, while the M2 polarization was promoted. Withdraw of the Notch signal inhibitor did not permit M2 N9 cells to re-polarize to M1 upon LPS stimulation, suggesting that the effects of Notch blockade on microglial polarization could be "memorized" by cells. These results suggest complicated mechanisms including epigenetic programs in the regulation of macrophage polarization. (C) 2012 Elsevier Inc. All rights reserved.