STRESS-IMMUNE-GROWTH INTERACTIONS IN RAINBOW TROUT: A ROLE FOR SUPPRESSORS OF CYTOKINE SIGNALING (SOCS)  

Mathilakath M. Vijayan* and Anju M. Philip
 
Department of Biological Sciences
University of Calgary
Calgary, AB
T2N1N4, Canada
matt.vijayan@ucalgary.ca
 

Chronic stress is a major factor in the poor growth and immune performance of salmonids in aquaculture. However, the molecular mechanisms linking stress effects to growth and immune dysfunction is poorly understood. The suppressors of cytokine signaling (SOCS) is a family of proteins involved in the inhibition of JAK/STAT pathway and negatively regulates growth hormone and cytokine signaling. However, the stress effect on SOCS regulation is far from clear. Here we tested the hypothesis that cortisol modulates SOCS gene expression and this is a key molecular mechanism leading to growth and immune suppression in response to stress in fish.

Precision cut rainbow trout (Oncorhynchus mykiss) liver slices were exposed to stress levels of cortisol for 24 h. This stress steroid upregulated SOCS-1 and SOCS-2 mRNA abundance, but this response was abolished by the glucocorticoid receptor (GR) antagonist mifepristone. Bioinformatics analysis supported the presence of putative glucocorticoid response elements in trout SOCS-1 and SOCS-2 promoters. Cortisol treatment suppressed growth hormone (GH)-stimulated IGF-1 mRNA abundance in trout liver and this involved a reduction in STAT5 phosphorylation and lower total JAK2 protein expression. Cortisol also suppressed lipopolysaccharide (LPS)-mediated increase in IL-6, but not IL-8 transcript levels; the former but not the latter cytokine expression is via JAK/STAT phosphorylation. LPS treatment reduced GH signaling, but this was associated with the downregulation of GH receptors and not due to the upregulation of SOCS transcript levels by this endotoxin.

Collectively, our results suggest that upregulation of liver SOCS-1 and SOCS-2 transcript levels by cortisol, and the associated reduction in JAK/STAT signaling pathway, may be a novel molecular mechanism linking stress effects on growth and immune suppression in fish.

This study was supported by the Natural Sciences and Engineering Research Council of Canada Discovery Grant to MMV.