Comparative Expression Analysis of Stress-Inducible Genes in Murine Immune Cells

Abstract

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.