Regulation of the rainbow trout spleen corticotropin-releasing factor system in response to inflammatory challenges: roles of NF-κB and cortisol.

The corticotropin-releasing factor (CRF) system bidirectionally interacts with cytokines and other immune-related components in mammals. However, the nature of these interactions remains poorly characterized in other vertebrates, including teleost fishes. To gain insight into the relationship between immune responses and the CRF system in teleosts, we explored how CRF system components were regulated in immune organs of rainbow trout (Oncorhynchus mykiss). We first characterized the CRF system in the spleen and head kidney-two primary immune organs in teleosts-and found that many CRF system components were present in both tissues, but splenic expression was consistently greater. Changes in the abundance of splenic CRF system transcripts following vaccination (which transiently stimulated inflammatory responses and cytokine production) indicated that this inflammatory challenge had contrasting and time-dependent effects on transcripts related to CRF receptor 1 (CRFR1; suppression) versus CRFR2 (stimulation). Using spleen explant cultures, we evaluated whether these effects were mediated by either of nuclear factor kappa B (NF-κB; a pro-inflammatory transcription factor) or cortisol (an anti-inflammatory hormone). At baseline, cultured spleens increased cytokine production and exhibited changes in mRNA levels of CRF system components comparable to those observed following vaccination. Cortisol treatment and NF-κB inhibition both attenuated the rise in cytokine mRNA levels; however, cortisol treatment generally affected transcripts related to CRFR1, while NF-κB inhibition reduced levels of transcripts related to CRFR2. Overall, our data provide novel insight into CRF system regulation in the spleen and suggest that cortisol and inflammatory cytokines differentially regulate CRFR1 and CRFR2 signalling within this organ.