Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.
Chronic exposure to exogenous glucocorticoids primes microglia to pro-inflammatory stimuli and induces NLRP3 mRNA in the hippocampus.
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DOI：
10.1016/j.psyneuen.2013.11.006
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发表时间：
2014-02
影响因子：
3.7
通讯作者：
Maier, Steven F.
中科院分区：
文献类型：
--
作者：
Frank, Matthew G.;Hershman, Sarah A.;Weber, Michael D.;Watkins, Linda R.;Maier, Steven F.
慢性应激以及糖皮质激素（GC）的慢性治疗引发了随后促炎性挑战的神经炎症反应。然而，尚不清楚慢性GC是否使关键CNS免疫底物（即小胶质细胞）对促炎刺激的反应敏感。在本研究中，雄性Sprague-Dawley大鼠接受假手术或肾上腺切除术，然后在其饮用水中给予不同浓度的皮质酮（CORT; 0、25、50和75 ug/ml）。在CORT暴露10天后，收集整个海马并测量胶质细胞活化标志物的表达，或者分离海马小胶质细胞并用LPS激发以探测CORT诱导的促炎反应的敏化。慢性CORT暴露以浓度依赖性方式增加NLRP 3、Iba-1、MHCII和NF-κBIα的基因表达。与用溶剂处理的假手术动物的小胶质细胞反应相比，慢性CORT（75 ug/ml）暴露增强了小胶质细胞对LPS的促炎反应（TNFα、IL-1β、IL-6和NLRP 3）。目前的一组结果表明，长期暴露于GC引发小胶质细胞的促炎刺激，并增加了越来越多的证据表明，GC的容许功能是内源性危险信号或报警。
Chronic stress as well as chronic treatment with glucocorticoids (GCs) primes the neuroinflammatory response to a subsequent pro-inflammatory challenge. However, it remains unclear whether chronic GCs sensitize the response of key CNS immune substrates (i.e. microglia) to pro-inflammatory stimuli. In the present set of studies, male Sprague-Dawley rats underwent sham surgery or were adrenalectomized and then treated with varying concentrations of corticosterone (CORT; 0, 25, 50, and 75 ug/ml) administered in their drinking water. After 10d of CORT exposure, whole hippocampus was collected and expression of glial activation markers measured or hippocampal microglia were isolated and challenged with LPS to probe for CORT-induced sensitization of pro-inflammatory responses. Chronic CORT exposure increased the gene expression of NLRP3, Iba-1, MHCII, and NF-κBIα in a concentration dependent manner. Chronic CORT (75 ug/ml) exposure potentiated the microglial proinflammatory response (TNFα, IL-1β, IL-6 and NLRP3) to LPS compared to the microglial response of sham surgery animals treated with vehicle. The present set of results demonstrate that chronic exposure to GCs primes microglia to pro-inflammatory stimuli and add to a growing body of evidence suggesting that a permissive function of GCs is that of an endogenous danger signal or alarmin.
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影响因子：
4.8
作者：
Lannan, Erica A.;Galliher-Beckley, Amy J.;Cidlowski, John A.
通讯作者：
Cidlowski, John A.
影响因子：
5.3
作者：
Munhoz, Carolina Demarchi;Sorrells, Shawn F.;Sapolsky, Robert M.
通讯作者：
Sapolsky, Robert M.
影响因子：
15.1
作者：
Johnson, JD;O'Connor, KA;Maier, SF
通讯作者：
Maier, SF
影响因子：
4.7
作者：
Kelly KA;Miller DB;Bowyer JF;O'Callaghan JP
通讯作者：
O'Callaghan JP
影响因子：
5.4
作者：
Hornung, Veit;Latz, Eicke
通讯作者：
Latz, Eicke