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| Glucocorticoid-mediated repression of NF kappa B activity in endothelial cells does not involve induction of I kappa B alpha synthesis |
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| Author(s): Brostjan C, Anrather J, Csizmadia V, Stroka D, Soares M, Bach FH, Winkler H |
| Source: JOURNAL OF BIOLOGICAL CHEMISTRY Volume: 271 Issue: 32 Pages: 19612-19616 Published: AUG 9 1996 |
| Times Cited: 158 References: 36 |
| Abstract: 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Brostjan, C (reprint author), HARVARD UNIV, SCH MED, DEACONESS HOSP, SANDOZ CTR IMMUNOBIOL, 99 BROOKLINE AVE, BOSTON, MA 02215 USA |
| Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 |
| Subject Category: Biochemistry & Molecular Biology |
| IDS Number: VB684 |
| ISSN: 0021-9258 |
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