Witek Emily, Hickman Debra, Lahiri Debomoy K, Srinivasan Mythily
Laboratory Animal Resources and Center, Department of Internal Medicine, Indiana University School of Medicine, Indianapolis, IN, United States.
Department of Psychiatry, Stark Neuroscience Research Institute, Indiana University School of Medicine, Indianapolis, IN, United States.
Front Aging Neurosci. 2019 Jan 25;10:432. doi: 10.3389/fnagi.2018.00432. eCollection 2018.
Glucocorticoids (GCs) are steroid hormones secreted as the end-product of the neuroendocrine stress cascade. Both absence and elevated GC mediate neurotoxic responses, suggesting that a narrow window ranging from physiological to slightly high GC mediate protective responses. The beneficial effects of GC are attributed to the transactivation of regulatory proteins and inhibition mediated by glucocorticoid receptor (GR) interactions with other co-factors. The glucocorticoid induced leucine zipper (GILZ) is a gene strongly upregulated by GC and mediates many of the anti-inflammatory and anti-proliferative effects of GC. Although GILZ is constitutively expressed in many tissues including the brain, the expression has been shown to occur with varying dynamics suggesting that the local milieu modulates its expression with consequent effects on cellular responses. Here we investigated the expression profile of GILZ in lipopolysaccharide (LPS) mediated neuroinflammation model of Alzheimer's disease (AD). Our data suggest that the GILZ expression is downregulated in neuroinflammation correlating inversely with the pro-inflammatory cytokines and innate immune responses.
糖皮质激素（GCs）是作为神经内分泌应激级联反应的终产物分泌的类固醇激素。GC缺乏和升高都会介导神经毒性反应，这表明从生理水平到略高于生理水平的窄范围GC介导保护性反应。GC的有益作用归因于调节蛋白的反式激活以及糖皮质激素受体（GR）与其他辅助因子相互作用介导的抑制作用。糖皮质激素诱导亮氨酸拉链（GILZ）是一种受GC强烈上调的基因，并介导GC的许多抗炎和抗增殖作用。尽管GILZ在包括大脑在内的许多组织中组成性表达，但已表明其表达具有不同的动态变化，这表明局部微环境调节其表达，从而对细胞反应产生影响。在此，我们研究了GILZ在脂多糖（LPS）介导的阿尔茨海默病（AD）神经炎症模型中的表达谱。我们的数据表明，GILZ表达在神经炎症中下调，与促炎细胞因子和先天免疫反应呈负相关。
