Glucocorticoid-mediated Repression of NFκB Activity in Endothelial Cells Does Not Involve Induction of IκBα Synthesis

• Published in: The Journal of biological chemistry Vol. 271; no. 32; pp. 19612 - 19616
• Main Authors: Brostjan, Christine, Anrather, Josef, Csizmadia, Vilmos, Stroka, Deborah, Soares, Miguel, Bach, Fritz H., Winkler, Hans
• Format: Journal Article
• Language: English
• Published: 1996
• ISSN: 0021-9258
• DOI: 10.1074/jbc.271.32.19612

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 . We 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.