Role of transcriptional activation of I in mediation of immunosuppression by glucocorticoids

Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-[kappa]B), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-[kappa]B involves the targeted...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 1995-10, Vol.270 (5234), p.283
Main Authors: Scheinman, Robert I, Cogswell, Patricia C, Lofquist, Alan K, Baldwin, Jr., Albert S
Format: Article
Language:English
Subjects:
Immune response
Immune response regulation
Immunosuppression
Immunosuppressive agents
Regulation
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Summary:Glucocorticoids are potent immunosuppressive drugs, but their mechanism is poorly understood. Nuclear factor kappa B (NF-[kappa]B), a regulator of immune system and inflammation genes, may be a target for glucocorticoid-mediated immunosuppression. The activation of NF-[kappa]B involves the targeted degradation of its cytoplasmic inhibitor, I[kappa]B[alpha], and the translocation of NF-[kappa]B to the nucleus. Here it is shown that the synthetic glucocorticoid dexamethasone induces the transcription of the I[kappa]B[alpha] gene, which results in an increased rate of I[kappa]B[alpha] protein synthesis. Stimulation by tumor necrosis factor causes the release of NF-[kappa]B from I[kappa]B[alpha]. However, in the presence of dexamethasone this newly released NF-[kappa]B quickly reassociates with newly synthesized I[kappa]B[alpha], thus markedly reducing the amount of NF-[kappa]B that translocates to the nucleus. This decrease in nuclear NF-[kappa]B is predicted to markedly decrease cytokine secretion and thus effectively block the activation of the immune system.
ISSN:0036-8075
1095-9203