Prion protein participates in the regulation of classical and alternative activation of BV2 microglia
Prion protein participates in the regulation of classical and alternative activation of BV2 microglia
复制标题
朊病毒蛋白参与 BV2 小胶质细胞经典激活和替代激活的调节
DOI：
10.1111/jnc.12053
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发表时间：
2013-01-01
影响因子：
4.7
通讯作者：
Zhao, Deming
中科院分区：
文献类型：
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作者：
Shi, Fushan;Yang, Lifeng;Zhao, Deming
细胞朊蛋白（PrPC）是一种由糖基磷脂酰肌醇（GPI）锚定在细胞表面的糖蛋白，在中枢神经系统中大量表达。许多研究表明PrPC具有保护功能，包括保护缺血性和兴奋性毒性病变以及几种凋亡损伤，最近的报告表明PrPC具有环境依赖性神经保护功能。在这项研究中，我们研究了PPNP下调对各种形式的小胶质细胞活化的影响。我们首先检查了BV 2小胶质细胞中暴露于IFN-γ、IL-4或IL-10后PRNP的mRNA表达。然后，我们分析了si-RNA介导的PRNP破坏对IFN-γ、IL-4或IL-10刺激的小胶质细胞中小胶质细胞活化的不同参数的影响。结果显示，暴露于IFN-γ、IL-4或IL-10后，PRNP mRNA表达在小胶质细胞中总是下调。细胞因子处理前PRNP沉默降低了小胶质细胞对INF-γ处理的反应性，显著改变了IL-4诱导的小胶质细胞活化表型，对IL-10诱导的小胶质细胞活化没有影响。总之，这些结果支持的作用，PrPC在调制的小胶质细胞从静止状态到激活表型的转变，并在经典和替代激活过程中的小胶质细胞反应的调节。
The cellular prion protein (PrPC) is a glycoprotein anchored by glycosylphosphatidylinositol (GPI) to the cell surface and is abundantly expressed in the central nervous system. Numerous studies have suggested a protective function for PrPC, including protection from ischemic and excitotoxic lesions and several apoptotic insults, and recent reports have shown that PrPC has a context‐dependent neuroprotective function. In this study, we investigated the effect of PPNP down‐regulation on various forms of microglial activation. We first examined the mRNA expression of PRNP upon exposure to IFN‐γ, IL‐4, or IL‐10 in BV2 microglia. We then analyzed the effect of si‐RNA‐mediated disruption of PRNP on different parameters of microglial activation in IFN‐γ‐, IL‐4‐, or IL‐10‐stimulated microglia. The results showed that PRNP mRNA expression was invariably down‐regulated in microglia upon exposure to IFN‐γ, IL‐4, or IL‐10. PRNP silencing prior to cytokines treatment reduced the responsiveness of microglia to INF‐γ treatment, significantly altered IL‐4‐induced microglial activation phenotype, and had no effect on IL‐10‐induced microglial activation. Together, these results support a role of PrPC in the modulation of the shift of microglia from a quiescent state to an activated phenotype and in the regulation of the microglial response during classical and alternative activation.