Corticotropin Releasing Factor (CRF) activation of NF-kappaB-directed transcription in leukocytes.

1. The aim of this study was to test whether CRF enhanced nuclear factor kappa B (NF-kappaB)-directed gene transcription in leukocytes and the receptor specificity of the effect. Initially, we examined the ability of CRF to modulate an antigen-specific, in vitro antibody response. Since that could be mediated by NF-kappaB transcription factor activity, we tested CRF in a NF-kappaB driven luciferase gene expression reporter assay. 2. CRF enhanced the antigen-specific antibody production in a dose- and time-dependent manner. RAW 264.7 macrophage cells and splenocytes stained by immunohistochemistry were positive for CRF receptors and CRF. Expression of both was up-regulated by mitogen treatment of the splenocytes. CRF also enhanced the NF-kappaB-regulated reporter assay and this could be blocked by a CRF-R1 receptor antagonist. 3. In light of these findings, it seems likely that CRF enhanced the antigen-specific antibody response through the CRF-R1 receptor by elevation of NF-kappaB activity. This study provides further support for the concept that CRF can act as an immunomodulator mediating neuro-immune interactions.