Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner
Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner
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DOI：
10.1523/jneurosci.0303-09.2010
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发表时间：
2010-10-13
影响因子：
5.3
通讯作者：
Sapolsky, Robert M.
中科院分区：
文献类型：
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作者：
Munhoz, Carolina Demarchi;Sorrells, Shawn F.;Sapolsky, Robert M.
虽然糖皮质激素（GC）的抗炎作用是公认的，但越来越多的证据表明，促炎性GC效应可以在大脑中发生，但其方式知之甚少。利用电泳迁移率变动分析、实时PCR和免疫印迹，我们研究了不同浓度的皮质酮（CORT，大鼠的GC）调节脂多糖（LPS）诱导的NF-κ B B活化（核因子kappa B）、抗炎因子和促炎因子以及MAP的表达（促分裂原活化蛋白）激酶家族[ERK（细胞外信号调节激酶）、p38和JNK/ SAPK（c-Jun N-末端蛋白激酶/应激活化蛋白激酶）]和AKT。在额叶皮质，升高的CORT水平是促炎性的，加重了LPS对NF-κ B B、MAP激酶和促炎基因表达的影响。轻度的促炎GC的影响发生在海马。在没有LPS的情况下，升高的CORT水平增加了两个区域中ERK 1/ 2、p38、SAPK/ JNK和AKT的基础激活。这些发现表明，GC不能均匀地抑制神经炎症，甚至可以在连接LPS暴露与炎症的通路中的多个水平上增强它。
Although the anti-inflammatory actions of glucocorticoids (GCs) are well established, evidence has accumulated showing that proinflammatory GC effects can occur in the brain, in a poorly understood manner. Using electrophoretic mobility shift assay, real-time PCR, and immunoblotting, we investigated the ability of varying concentrations of corticosterone (CORT, the GC of rats) to modulate lipopolysaccharide (LPS)-induced activation of NF-kappa B (nuclear factor kappa B), expression of anti- and proinflammatory factors and of the MAP (mitogen-activated protein) kinase family [ERK (extracellular signal-regulated kinase), p38, and JNK/ SAPK (c-Jun N-terminal protein kinase/ stress-activated protein kinase)], and AKT. In the frontal cortex, elevated CORT levels were proinflammatory, exacerbating LPS effects on NF-kappa B, MAP kinases, and proinflammatory gene expression. Milder proinflammatory GCs effects occurred in the hippocampus. In the absence of LPS, elevated CORT levels increased basal activation of ERK1/ 2, p38, SAPK/ JNK, and AKT in both regions. These findings suggest that GCs do not uniformly suppress neuroinflammation and can even enhance it at multiple levels in the pathway linking LPS exposure to inflammation.