Dexamethasone attenuates NF-kappa B DNA binding activity without inducing I kappa B levels in rat brain in vivo

This investigation tested if glucocorticoid hormones modulate activation of the NF-KB transcription factor in rat brain in vivo. Dexamethasone (2 mg/kg) administration decreased NF-KB DNA binding in cerebral cortex and hippocampus nuclear extracts, maximally at 3-6 h after dexamethasone, followed by recovery at 24 h. Dexamethasone did not inhibit NF-KB by increasing the level of the inhibitory protein I kappa B alpha, as occurs in some peripheral cells, but instead lowered I kappa B alpha levels. Direct protein-protein inhibition by glucocorticoids was indicated by co-precipitation of glucocorticoid receptors with the p65 NF-KB subunit. Thus, glucocorticoids inhibit NF-kappa B DNA binding in rat brain, apparently by complexing with NF-kappa B subunits, which may contribute to the detrimental effects of glucocorticoids on neuronal function associated with oxidative stress and excitotoxicity.