Effects of glucocorticoid receptor activation on gene expression and antiviral responses in Atlantic salmon (Salmo salar L.) red blood cells.

Farmed Atlantic salmon are subjected to different stressors during management routines, leading to prolonged elevated cortisol levels in the blood, a hallmark of chronic stress responses. In this study, we investigate how dexamethasone, an agonist for glucocorticoid receptors (GRs), and cortisol, an endogenous glucocorticoid, regulate gene expression in isolated A. salmon red blood cells (RBCs). Salmonid RBCs express GR genes at high levels. Transcriptional analysis revealed that dexamethasone significantly upregulated 156 genes, and led to > 100-fold induction of the genes FKBP prolyl isomerase 5 (fkbp5), the Krueppel-like factor 9 (klf9), and the DNA damage-inducible transcript 4 (ddit4). The significant upregulation of fkbp5 persisted for up to two weeks post RBC stimulation, indicating its potential as a biomarker candidate for chronic stress exposure. We compared ex vivo transcriptional responses in RBCs with responses in blood cells from A. salmon injected intraperitoneally with hydrocortisone, and found that ddit4 may be the most promising biomarker candidate for stress response in vivo. Dexamethasone and cortisol also downregulated antiviral and proteasome genes triggered by double-stranded RNA in RBCs. The results indicate that glucocorticoids have a profound effect on gene expression and putatively alter functions of A. salmon RBCs, and particularly block the antiviral response.