Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis.

Cytokine and chemokine responses in serum and brain after single and repeated injections of lipopolysaccharide: multiplex quantification with path analysis.
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DOI:
10.1016/j.bbi.2011.06.006
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发表时间:
2011-11
影响因子:
15.1
通讯作者:
Banks, William A.
Banks, William A.
中科院分区:
医学1区
文献类型:
--
作者:
Erickson, Michelle A.;Banks, William A.

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促炎分子脂多糖 (LPS) 的施用会改变许多肽穿过血脑屏障 (BBB) 的转运速率。我们和其他人之前已经表明,LPS 对 BBB 转运的影响高度依赖于所使用的注射范例和研究时间。大脑和血清区室中的细胞因子表达影响 BBB 对炎症刺激的反应,并介导 BBB 转运的变化。在这里,我们使用多分析物技术同时测定脑和血液中 13 种细胞因子和趋化因子(G-CSF、GM-CSF、IL-1α、IL-1β、IL-6、IL-10、IL-13、IP-10、KC、MCP-1、MIP-1α、RANTES 和 TNF-α)对单次和重复注射 LPS 的反应,并进行路径分析以确定它们之间的主要关系。 这些分析物。主要发现是:1) 与单次注射 LPS 后的时间过程测量相比,LPS 的三种注射方案在大脑中产生显着更高的 G-CSF、IL-1 α、IL-6、MCP-1、MIP-1 α 和 TNF 水平,以及在血清中的 G-CSF、IL-6 和 GM-CSF 水平显着更高;2) 路径分析区分了分析物之间的直接相关性和间接相关性 与 MCP-1、IL-6、G-CSF 和 KC 配对,介导血清和脑区室内及之间的这些细胞因子之间的关系。这些结果表明,大脑和血清区室中细胞因子水平的增强可能在 BBB 运输的调节中发挥重要作用,并且我们对已建立的统计方法的新应用可用于评估多重数据集中的直接相关性。
Administration of the proinflammatory molecule lipopolysaccharide (LPS) alters transport rates for many peptides across the blood-brain barrier (BBB). We and others have previously shown that effects of LPS on BBB transport are highly dependent on the injection paradigm used, and timing of the study. Cytokine expression in both brain and serum compartments influence the BBB response to an inflammatory stimulus, and mediate changes in BBB transport. Here, we used multianalyte technology to simultaneously determine the responses of 13 cytokines and chemokines (G-CSF, GM-CSF, IL- 1α, IL-1β, IL-6, IL-10, IL-13, IP-10, KC, MCP-1, MIP-lα, RANTES, and TNF- α) in brain and blood to single and repeated injections of LPS and path analysis to determine the major relations among these analytes. Major findings are: 1) in comparison to measurements taken from a time course after a single injection of LPS, the three injection regimen of LPS produced significantly higher levels in brain for G-CSF, IL-1 alpha, IL-6, MCP-1, MIP-1 alpha, and TNF and in serum for G-CSF, IL-6, and GM-CSF and 2) path analysis distinguished direct from indirect correlations between analyte pairs, with MCP-1, IL-6, G-CSF, and KC mediating relations among these cytokines both within and between serum and brain compartments. These results suggest that potentiation of cytokine levels in brain and serum compartments could play important roles in the regulation of BBB transport, and that our novel application of an established statistical method can be used to assess direct correlations within multiplexed datasets.
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