Glucocorticoid-mediated repression of NF kappa B activity in endothelial cells does not involve induction of I kappa B alpha synthesis

Repression of NF kappa B-dependent gene expression is one of the major elements of immunosuppression by glucocorticoids. Protein-protein interactions between the glucocorticoid receptor and NF kappa B have been characterized and shown to be a possible mechanism of mutual inhibition of transactivation properties, More recently, glucocorticoid-mediated induction of I kappa B alpha, an inhibitor of NF kappa B, has been described in monocytes and lymphocytes; an increase in I kappa B alpha mRNA and protein resulted in inactivation and cytosolic retention of NF kappa B, Thus, rather than the physical interaction between the glucocorticoid receptor and NF kappa B, the up-regulation of I kappa B alpha was presented as the key element in immunosuppression by glucocorticoids. in contrast, we show that the I kappa B alpha pathway is not involved in glucocorticoid-mediated inhibition of NF kappa B activity in endothelial cells, Although transcriptional activation by NF kappa B was significantly reduced in the presence of glucocorticoids, we did not detect induction of I kappa B alpha protein that could prevent nuclear translocation of NF kappa B upon stimulation with lipopolysaccharide or tumor necrosis factor alpha, Furthermore, treatment with glucocorticoids did not seem to affect the transcription rate or mRNA stability of I kappa B alpha. Ne therefore conclude that, although induction of I kappa B alpha expression by glucocorticoids seems to be of importance in monocytes and lymphocytes, it cannot explain inhibition of NF kappa B-dependent gene expression in endothelial cells. Our results emphasize the relevance of physical interaction between the glucocorticoid receptor and NF kappa B in endothelial cells and thus in suppression of inflammation by glucocorticoids.