Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells
Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells
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DOI：
10.1080/08820139.2019.1702673
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发表时间：
2019-12
影响因子：
2.8
通讯作者：
M. Koyanagi;Y. Arimura
中科院分区：
文献类型：
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作者：
M. Koyanagi;Y. Arimura
背景：心理应激影响免疫系统。应激发生时，释放糖皮质激素，与糖皮质激素受体结合，调节基因表达。因此，我们旨在通过研究应激诱导基因在小鼠免疫细胞中的表达模式来探讨应激诱导的免疫调节机制。方法：将BALB/c、C57BL/6、糖皮质激素受体基因型小鼠和促肾上腺皮质激素释放激素（CRH）缺陷小鼠分别暴露于合成糖皮质激素、地塞米松或约束条件下。检测应激相关基因Rtp801、Gilz、Mkp-1、Bnip3、Trp53inp1在这些小鼠免疫细胞中的表达水平。结果：短约束应激诱导的Rtp801和Gilz在BALB/c小鼠脾脏中的表达高于C57BL/6小鼠。尽管糖皮质激素水平不同，但Mkp-1表达在两株中均有增加。短约束应激诱导的这三个基因在crh缺陷小鼠中未被诱导。相比之下，Bnip3和Trp53inp1仅在较长时间的抑制事件中上调。在胸腺中，Trp53inp1的表达在短时间抑制应激下被诱导，而Gilz的表达在短时间和重复抑制应激下不断增加。结论：单次和反复应激导致小鼠基因表达差异，胸腺细胞中应激诱导的基因表达与脾细胞中不同。短约束应激诱导的Gilz、Rtp801和Mkp-1基因依赖于脾脏的CRH。
ABSTRACT Background: Psychological stress affects the immune system. Upon stress occurrence, glucocorticoid is released that binds to the glucocorticoid receptor and regulates gene expression. Thus, we aimed to examine the stress-induced immunomodulatory mechanisms by investigating the expression patterns of stress-inducible genes in murine immune cells. Methods: BALB/c, C57BL/6, glucocorticoid-receptor congenic mice, and corticotropin-releasing hormone (CRH)-deficient mice were exposed to synthetic glucocorticoid, dexamethasone, or placed under a restraint condition. The expression level of stress-related genes, such as Rtp801, Gilz, Mkp-1, Bnip3, and Trp53inp1 was measured in the immune cells in these mice. Results: Short restraint stress induced Rtp801 and Gilz expressions that were higher in the spleen of BALB/c mice than those in C57BL/6 mice. Mkp-1 expression increased equally in these two strains, despite the difference in the glucocorticoid level. These three genes induced by short restraint stress were not induced in the CRH-deficient mice. In contrast, Bnip3 and Trp53inp1 were only upregulated upon longer restraint events. In the thymus, Trp53inp1 expression was induced upon short restraint stress, whereas Gilz expression constantly increased upon short and repetitive restraint stresses. Conclusion: These results suggest that singular and repetitive bouts of stress lead to differential gene expression in mice and stress-induced gene expression in thymocytes is distinct from that observed in splenocytes. Gilz, Rtp801, and Mkp-1 genes induced by short restraint stress are dependent on CRH in the spleen.