Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines.
Peripheral lipopolysaccharide (LPS) challenge promotes microglial hyperactivity in aged mice that is associated with exaggerated induction of both pro-inflammatory IL-1beta and anti-inflammatory IL-10 cytokines.
复制标题
DOI：
10.1016/j.bbi.2008.09.002
复制
发表时间：
2009-03
影响因子：
15.1
通讯作者：
Godbout, Jonathan P.
中科院分区：
文献类型：
--
作者：
Henry, Christopher J.;Huang, Yan;Wynne, Angela M.;Godbout, Jonathan P.
在老年人中，全身感染与行为和认知并发症发生频率增加有关。我们已经报道，脂多糖（LPS）对先天免疫系统的外周刺激会导致老年 BALB/c 小鼠出现过度的神经炎症反应和长期的疾病/抑郁样行为。因此，本研究的目的是确定 LPS 诱导的神经炎症与小胶质细胞特异性诱导神经炎症介质的相关程度。在这里，我们发现外周 LPS 激发会导致衰老大脑中小胶质细胞过度活跃，并与炎症性 IL-1β 和抗炎性 IL-10 的较高诱导相关。与成年小鼠相比，LPS 注射可显着诱导老年小鼠皮质中 IL-1β 和 IL-10 mRNA 的表达。在下一组研究中，在实验治疗后从成年和老年小鼠的大脑中分离出小胶质细胞（CD11b+/CD45low）。在小胶质细胞中检测到主要组织相容性复合物 (MHC) II 类 mRNA 和蛋白质表达随年龄的增加。此外，外周 LPS 注射导致老年小鼠小胶质细胞中 IL-1β、IL-10、Toll 样受体 (TLR)-2 和吲哚胺 2, 3 双加氧酶 (IDO) mRNA 水平比成年小鼠更显着增加。细胞内细胞因子蛋白检测证实，外周脂多糖引起老年小鼠小胶质细胞中IL-1β和IL-10水平的最高增加。最后，在老年小鼠的 MHC II+ 小胶质细胞中检测到最显着的 IL-1β 诱导作用。总而言之，这些发现提供了新的证据，表明与年龄相关的小胶质细胞启动在外周先天免疫系统激活引起的过度神经炎症中发挥着核心作用。
In the elderly, systemic infection is associated with an increased frequency of behavioral and cognitive complications. We have reported that peripheral stimulation of the innate immune system with lipopolysaccharide (LPS) causes an exaggerated neuroinflammatory response and prolonged sickness/depressive-like behaviors in aged BALB/c mice. Therefore, the purpose of this study was to determine the degree to which LPS-induced neuroinflammation was associated with microglia-specific induction of neuroinflammatory mediators. Here, we show that peripheral LPS challenge caused a hyperactive microglial response in the aged brain associated with higher induction of inflammatory IL-1β and anti-inflammatory IL-10. LPS injection caused a marked induction of mRNA expression of both IL-1β and IL-10 in the cortex of aged mice compared to adults. In the next set of studies, microglia (CD11b+/CD45low) were isolated from the brain of adult and aged mice following experimental treatments. An age-dependent increase in major histocompatibility complex (MHC) class II mRNA and protein expression was detected in microglia. Moreover, peripheral LPS injection caused a more pronounced increase in IL-1β, IL-10, Toll-like Receptor (TLR)-2, and indoleamine 2, 3 dioxygenase (IDO) mRNA levels in microglia isolated from aged mice than adults. Intracellular cytokine protein detection confirmed that peripheral LPS caused the highest increase in IL-1β and IL-10 levels in microglia of aged mice. Finally, the most prominent induction of IL-1β was detected in MHC II+ microglia from aged mice. Taken together, these findings provide novel evidence that age-associated priming of microglia plays a central role in exaggerated neuroinflammation induced by activation of the peripheral innate immune system.
登录
查看更多内容
DOI：
10.1016/s0169-328x(00)00042-5
发表时间：
2000-04-14
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Heyen, JRR;Ye, SM;Johnson, RW
通讯作者：
Johnson, RW
影响因子：
15.1
作者：
Chen, Jing;Buchanan, Jessica B.;Johnson, Rodney W.
通讯作者：
Johnson, Rodney W.
DOI：
10.2165/00129785-200404050-00005
发表时间：
2004-01-01
期刊：
American journal of pharmacogenomics : genomics-related research in drug development and clinical practice
影响因子：
--
作者：
Carson, Monica J;Thrash, J Cameron;Lo, David
通讯作者：
Lo, David
影响因子：
5.5
作者：
Chelvarajan, R. Lakshman;Liu, Yushu;Bondada, Subbarao
通讯作者：
Bondada, Subbarao
影响因子：
5.5
作者：
Chelvarajan, RL;Collins, SM;Bondada, S
通讯作者：
Bondada, S