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Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids

Science
13 Oct 1995
Vol 270, Issue 5234
pp. 283-286

Abstract

Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-κB), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-κB involves the targeted degradation of its cytoplasmic inhibitor, IκBα, and the translocation of NF-κB to the nucleus. Here it is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the IκBα gene, which results in an increased rate of IκBα protein synthesis. Stimulation by tumor necrosis factor causes the release of NF-κB from IκBα. However, in the presence of dexamethasone this newly released NF-κB quickly reassociates with newly synthesized IκBα, thus markedly reducing the amount of NF-κB that translocates to the nucleus. This decrease in nuclear NF-κB is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.

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Information & Authors

Information

Published In

Science
Volume 270 | Issue 5234
13 October 1995

Submission history

Published in print: 13 October 1995

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Authors

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Robert I. Scheinman(1)
R. I. Scheinman, P. C. Cogswell, A. K. Lofquist, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Patricia C. Cogswell
R. I. Scheinman, P. C. Cogswell, A. K. Lofquist, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Alan K. Lofquist(2)
R. I. Scheinman, P. C. Cogswell, A. K. Lofquist, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
Albert S. Baldwin, Jr.(3)
A. S. Baldwin Jr., Lineberger Comprehensive Cancer Center and Department of Biology, University of North Carolina, Chapel Hill, NC 27599, USA.

Notes

(1)
Present address: School of Pharmacy, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
(2)
Present address: Department of Biological Science, University of Idaho, Moscow, ID 80844, USA.
(3)
To whom correspondence should be addressed.

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  1. Hypothalamic circuitry underlying stress-induced insomnia and peripheral immunosuppression, Science Advances, 6, 37, (2020)./doi/10.1126/sciadv.abc2590
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  2. Immunosuppression by Glucocorticoids: Inhibition of NF-κB Activity Through Induction of IκB Synthesis, Science, 270, 5234, (286-290), (1995)./doi/10.1126/science.270.5234.286
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