Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1β.
Age-associated alterations in the time-dependent profile of pro- and anti-inflammatory proteins within the hippocampus in response to acute exposure to interleukin-1β.
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DOI：
10.1016/j.jneuroim.2013.12.010
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发表时间：
2014-02-15
影响因子：
3.3
通讯作者：
Wenk, Gary L.
中科院分区：
文献类型：
--
作者：
Hopp, Sarah C.;Royer, Sarah;Brothers, Holly M.;Kaercher, Roxanne M.;D'Angelo, Heather;Bardou, Isabelle;Wenk, Gary L.
已知促炎细胞因子IL-1β在衰老、神经炎症和神经退行性疾病的几种模型中发挥作用。在此，我们记录了双侧海马内注射白细胞介素-1 β后促炎和抗炎生物标志物的时间和年龄依赖性模式。在前12小时期间，几种促炎和抗炎细胞因子在老年（24月龄）大鼠中增加，其中一些在注射后24小时恢复到基线水平，而另一些在注射后72小时保持升高。相比之下，在年轻（3月龄）大鼠中未观察到此类增加。有趣的是，幼年大鼠上调了IL-1β和TNF-α两种促炎细胞因子的mRNA，但未将其翻译成功能蛋白，这可能与细胞因子信号转导抑制因子2的表达有关。这些结果有助于我们了解神经炎症如何可能有助于年龄相关的神经退行性疾病的发病机制，由于年龄相关的偏见对高反应性免疫反应，这是不选择性的促炎或抗炎表型后的炎症刺激。
The pro-inflammatory cytokine IL-1β is known to play a role in several models of aging, neuroinflammation, and neurodegenerative diseases. Here, we document a detailed time- and age-dependent pattern of pro- and anti-inflammatory biomarkers following bilateral intrahippocampal injection of interleukin-1β. During the first 12 hours several pro- and anti-inflammatory cytokines increased in the aged (24 mo old) rats, some of which returned to baseline levels by 24 hours post-injection while others remained elevated for 72 hours post-injection. In contrast, no such increases were observed in the young (3 mo old) rats. Interestingly, young rats up-regulated mRNA of two pro-inflammatory cytokines, interleukin-1β and tumor necrosis factor-α, but did not translate these transcripts into functional proteins, which may be related to expression of suppressor of cytokine signaling type-2. These results contribute to our understanding of how neuroinflammation may contribute to the pathogenesis of age-related neurodegenerative disorders due to an age-related bias toward a hyper-reactive immune response that is not selective for a pro- or anti-inflammatory phenotype following an inflammatory stimulus.
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