Glucocorticoid signaling in myeloid cells worsens acute CNS injury and inflammation.
Glucocorticoid signaling in myeloid cells worsens acute CNS injury and inflammation.
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DOI：
10.1523/jneurosci.4705-12.2013
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发表时间：
2013-05-01
期刊：
影响因子：
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通讯作者：
Sapolsky RM
中科院分区：
文献类型：
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作者：
Sorrells SF;Caso JR;Munhoz CD;Hu CK;Tran KV;Miguel ZD;Chien BY;Sapolsky RM
糖皮质激素应激激素（GC）是众所周知的抗炎，但一些报告表明，GC也可以增加急性脑损伤期间的炎症方面。由于GC受体（GR）在整个大脑中普遍表达，因此很难知道哪些细胞类型可能介导这些不寻常的“促炎”GC作用。我们研究了这与细胞类型特异性缺失或过度表达的GR在小鼠经历癫痫发作或缺血。与其经典的抗炎作用相反，骨髓细胞中的GR信号增加了受损组织中的Iba-1和CD 68染色以及核p65水平。GC还降低了occludin，claudin 5和caveolin 1的水平，这些蛋白质对血脑屏障的完整性至关重要;这些作用需要内皮细胞中的GR。最后，GC损害神经元存活，在骨髓和内皮细胞中GR介导的效果比神经元GR更大程度。
Glucocorticoid stress hormones (GCs) are well known for being anti-inflammatory, but some reports suggest that GCs can also augment aspects of inflammation during acute brain injury. Because the GC receptor (GR) is ubiquitously expressed throughout the brain, it is difficult to know which cell types might mediate these unusual "pro-inflammatory" GC actions. We examined this with cell type-specific deletion or overexpression of GR in mice experiencing seizure or ischemia. Counter to their classical anti-inflammatory actions, GR signaling in myeloid cells increased Iba-1 and CD68 staining as well as nuclear p65 levels in the injured tissue. GCs also reduced levels of occludin, claudin 5, and caveolin 1, proteins central to blood-brain-barrier integrity; these effects required GR in endothelial cells. Finally, GCs compromised neuron survival, an effect mediated by GR in myeloid and endothelial cells to a greater extent than by neuronal GR.