Cortisol modulates the expression of cytokines and suppressors of cytokine signaling (SOCS) in rainbow trout hepatocytes

Although liver is a key target for corticosteroid action, its role in immune function is largely unknown. We tested the hypothesis that stress levels of cortisol down regulate immune-relevant genes in rainbow trout (Oncorhynchus mykiss) liver. Hepatocytes were treated with lipopolysaccharide (LPS) for 24 h either in the presence or absence of cortisol. LPS stimulated heat shock protein 70 expression, enhanced glycolytic capacity, and reduced glucose output. LPS stimulated mRNA abundance of cytokines and serum amyloid protein A (SAA), while suppressors of cytokine signaling (SOCS)-3 was reduced. Cortisol increased mRNA abundances of IL-1β, SOCS-1 and SOCS-2, while inhibiting either basal or LPS-stimulated IL-8, TNF α2 and SAA. These cortisol-mediated effects were rescued by Mifepristone, a glucocorticoid receptor antagonist. Altogether, cortisol modulates the molecular immune response in trout hepatocytes. The upregulation of SOCS-1 and SOCS-2 by cortisol may be playing a key role in suppressing cytokine signaling and the associated inflammatory response.

► LPS stimulation upregulates immune-responsive genes in trout hepatocytes.
► Stress-induced cortisol levels suppress the inflammatory response to LPS in hepatocytes.
► Cortisol upregulates the abundance of SOCS-1 and SOCS-2 mRNA in trout hepatocytes.
► Regulation of SOCS by cortisol may be involved in stress-mediated immune modulation.