Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels
Analysis of Protein Levels of 24 Cytokines in Scrapie Agent-Infected Brain and Glial Cell Cultures from Mice Differing in Prion Protein Expression Levels
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DOI：
10.1128/jvi.01413-09
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发表时间：
2009-11-01
影响因子：
5.4
通讯作者：
Chesebro, Bruce
中科院分区：
文献类型：
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作者：
Tribouillard-Tanvier, Deborah;Striebel, James F.;Chesebro, Bruce
小胶质细胞和星形胶质细胞的激活见于许多神经退行性疾病，包括朊病毒疾病。活化的神经胶质细胞产生细胞因子作为针对某些病原体的保护性反应，并且作为宿主对脑损伤的炎症反应的一部分。此外，细胞因子也可能加剧由其他过程引发的组织损伤。在目前的工作中，使用多重测定来分析痒病病原体感染的C57 BL/10小鼠脑中24种细胞因子的蛋白质水平，我们观察到CCL 2、CCL 5、CXCL 1、CXCL 10、粒细胞-巨噬细胞集落刺激因子（GM-CSF）、γ干扰素（IFN-γ）、白细胞介素1 α（IL-1 α）、IL-1 β、IL-6和IL-12 p40的升高。尽管在神经病理学方面存在广泛差异，但羊瘙痒病病原体感染的野生型小鼠和表达无锚朊蛋白（PrP）的转基因小鼠具有相似的细胞因子反应。因此，这些反应可能主要是对朊病毒感染引起的脑损伤的反应，而不是特定类型病理学的特异性诱导物。为了研究星形胶质细胞和小胶质细胞在这些细胞因子反应中的作用，将原代胶质细胞培养物暴露于羊瘙痒病病原体感染的脑匀浆中。小胶质细胞仅产生IL-12 p40和CXCL 10，而星形胶质细胞产生这些细胞因子以及CCL 2、CCL 3、CCL 5、CXCL 1、G-CSF、IL-1 β、IL-6、IL-12 p70和IL-13。神经胶质细胞因子反应野生型小鼠和转基因小鼠表达无锚PrP只有轻微的不同，但神经胶质细胞从PrP-null小鼠只产生IL-12 p40，这表明PrP的表达是所需的瘙痒症剂诱导检测到的其他细胞因子。小胶质细胞和星形胶质细胞之间细胞因子反应的差异与星形胶质细胞中PrP表达水平比小胶质细胞高20倍相关，表明星形胶质细胞上高水平的PrP表达可能对诱导某些细胞因子很重要。
Activation of microglia and astroglia is seen in many neurodegenerative diseases including prion diseases. Activated glial cells produce cytokines as a protective response against certain pathogens and as part of the host inflammatory response to brain damage. In addition, cytokines might also exacerbate tissue damage initiated by other processes. In the present work using multiplex assays to analyze protein levels of 24 cytokines in scrapie agent-infected C57BL/10 mouse brains, we observed elevation of CCL2, CCL5, CXCL1, CXCL10, granulocyte-macrophage colony-stimulating factor (GM-CSF), gamma interferon (IFN-gamma), interleukin 1 alpha (IL-1 alpha), IL-1 beta, IL-6, and IL-12p40. Scrapie agent-infected wild-type mice and transgenic mice expressing anchorless prion protein (PrP) had similar cytokine responses in spite of extensive differences in neuropathology. Therefore, these responses may be primarily a reaction to brain damage induced by prion infection rather than specific inducers of a particular type of pathology. To study the roles of astroglia and microglia in these cytokine responses, primary glial cultures were exposed to scrapie agent-infected brain homogenates. Microglia produced only IL-12p40 and CXCL10, whereas astroglia produced these cytokines plus CCL2, CCL3, CCL5, CXCL1, G-CSF, IL-1 beta, IL-6, IL-12p70, and IL-13. Glial cytokine responses from wild-type mice and transgenic mice expressing anchorless PrP differed only slightly, but glia from PrP-null mice produced only IL-12p40, indicating that PrP expression was required for scrapie agent induction of other cytokines detected. The difference in cytokine response between microglia and astroglia correlated with 20-fold-higher levels of PrP expression in astroglia versus microglia, suggesting that high-level PrP expression on astroglia might be important for induction of certain cytokines.