Differential Cytokine-Induced Responses of Polarized Microglia.
Differential Cytokine-Induced Responses of Polarized Microglia.
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极化小胶质细胞的分化细胞因子诱导反应。
DOI：
10.3390/brainsci11111482
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发表时间：
2021-11-10
期刊：
影响因子：
3.3
通讯作者：
Lokensgard JR
中科院分区：
文献类型：
--
作者：
Chauhan P;Sheng WS;Hu S;Prasad S;Lokensgard JR
选择促炎和抗炎介质的作用，在驱动小胶质细胞极化成经典（M1），或者，（M2）激活状态，以及随后的差异反应，这些诱导的表型，进行了检查。使用多色流式细胞术评估PD-L1、MHC-II、MHC-I、精氨酸酶1（Arg-1）和诱导型一氧化氮合酶（iNOS）的表达。我们观察到促炎和抗炎介质均诱导非极化小胶质细胞上的PD-L1表达。此外，IFN-γ刺激这些细胞上的MHC I类和II类显著表达。有趣的是，我们观察到只有IL-4处理才诱导Arg-1表达，表明M2极化。这些M2细胞对随后的去极化不敏感，并保持其交替激活状态。此外，在用促炎介质而不是抗炎细胞因子处理后，在这些M2极化小胶质细胞上显著诱导PD-L1表达。此外，我们观察到，只有LPS诱导小胶质细胞中的iNOS表达，表明M1极化。此外，IFN-γ显著增加表达iNOS的M1极化小胶质细胞的百分比。令人惊讶的是，当这些M1极化的小胶质细胞用IL-6或其他抗炎细胞因子处理时，它们恢复到它们的非极化状态，如通过显著降低的iNOS表达所证明的。两者合计，这些结果表明不同的微环境中存在的介质的小胶质细胞的差异反应。
The role of select pro- and anti-inflammatory mediators in driving microglial cell polarization into classically (M1), or alternatively, (M2) activated states, as well as the subsequent differential responses of these induced phenotypes, was examined. Expression of PD-L1, MHC-II, MHC-I, arginase 1 (Arg-1), and inducible nitric oxide synthase (iNOS) was assessed using multi-color flow cytometry. We observed that both pro- and anti-inflammatory mediators induced PD-L1 expression on non-polarized microglia. Moreover, IFN-γ stimulated significant MHC class I and II expression on these cells. Interestingly, we observed that only IL-4 treatment induced Arg-1 expression, indicating M2 polarization. These M2 cells were refractory to subsequent depolarization and maintained their alternatively activated state. Furthermore, PD-L1 expression was significantly induced on these M2-polarized microglia after treatment with pro-inflammatory mediators, but not anti-inflammatory cytokines. In addition, we observed that only LPS induced iNOS expression in microglial cells, indicating M1 polarization. Furthermore, IFN-γ significantly increased the percentage of M1-polarized microglia expressing iNOS. Surprisingly, when these M1-polarized microglia were treated with either IL-6 or other anti-inflammatory cytokines, they returned to their non-polarized state, as demonstrated by significantly reduced expression of iNOS. Taken together, these results demonstrate differential responses of microglial cells to mediators present in dissimilar microenvironments.
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影响因子：
5.3
作者：
Prasad S;Sheng WS;Hu S;Chauhan P;Lokensgard JR
通讯作者：
Lokensgard JR
影响因子：
9.3
作者：
Cherry JD;Olschowka JA;O'Banion MK
通讯作者：
O'Banion MK
T 细胞和肿瘤微环境之间的 IFN-gamma/PD-L1 轴：神经胶质瘤抗 PD-1/PD-L1 治疗的提示。
影响因子：
9.3
作者：
Qian J;Wang C;Wang B;Yang J;Wang Y;Luo F;Xu J;Zhao C;Liu R;Chu Y
通讯作者：
Chu Y
影响因子：
4.8
作者：
Kang, Jeong-Han;Jung, Mi-Yeon;Leof, Edward B.
通讯作者：
Leof, Edward B.
影响因子：
15.9
作者：
Herrero, C;Marqués, L;Celada, A
通讯作者：
Celada, A