The permissive role of glucocorticoids in neuroinflammatory priming: mechanisms and insights.
The permissive role of glucocorticoids in neuroinflammatory priming: mechanisms and insights.
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DOI：
10.1097/med.0000000000000168
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发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Maier SF
中科院分区：
文献类型：
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作者：
Frank MG;Watkins LR;Maier SF
糖皮质激素（GC）已被普遍认为是抗炎的，然而现在相当多的研究表明，在某些条件下，GC能够增强神经炎症过程（即引发），这是GC的容许功能。本文综述了最近的证据，提供了深入了解GC诱导的神经炎性启动的机制（S）。已经发现GC引发炎性小体（即NLRP 3），其是介导促炎过程的细胞内多蛋白复合物。炎症体被应激或受损细胞的产物激活。有趣的是，这些产物（损伤相关分子模式）是由应激诱导的，并介导应激诱导的神经炎症引发。鉴于这些发现，我们提出了一种GC诱导的神经炎性引发模型，其中应激和GC诱导脑中的细胞损伤/应激，其产物引发NLRP 3炎性体。因此，GC诱导的NLRP 3炎性体的引发可以介导对随后的促炎免疫攻击的增强的神经炎性应答。我们建议，在战斗/逃跑反应期间，可用的能量储存应该被转移到防御行为上，在紧急情况结束后，资源应该被转移到恢复和宿主防御感染上。这是通过升高的GC减少正在进行的炎症同时引发NLRP 3炎性体而促进的情况。
Glucocorticoids (GCs) have been universally regarded as anti-inflammatory, however a considerable number of studies now demonstrate that under some conditions, GCs are capable of potentiating neuroinflammatory processes (i.e. priming), a permissive function of GCs. The present review addresses recent evidence that provides insight into the mechanism(s) of GC-induced neuroinflammatory priming. GCs have been found to prime inflammasomes (i.e. NLRP3), which are intra-cellular multiprotein complexes that mediate pro-inflammatory processes. Inflammasomes are activated by products of stressed or damaged cells. Interestingly, these products (damage-associated molecular patterns) are induced by stress and mediate stress-induced neuroinflammatory priming. In light of these findings, we propose a model of GC-induced neuroinflammatory priming whereby stress and GCs induce cellular damage/stress in the brain, the products of which prime the NLRP3 inflammasome. Thus, GC-induced priming of the NLRP3 inflammasome may mediate the potentiated neuroinflammatory response to a subsequent pro-inflammatory immune challenge. We propose that during a fight/flight response available energy stores should be diverted to defensive behaviors, and it might be after the emergency is over that resources should be shifted to recuperation and host defense against infection. This is the scenario that would be promoted by elevated GCs reducing ongoing inflammation while simultaneously priming the NLRP3 inflammasome.