RT Journal Article
SR Electronic
T1 Role of Transcriptional Activation of IκBα in Mediation of Immunosuppression by Glucocorticoids
JF Science
JO Science
FD American Association for the Advancement of Science
SP 283
OP 286
DO 10.1126/science.270.5234.283
VO 270
IS 5234
A1 Scheinman, Robert I.
A1 Cogswell, Patricia C.
A1 Lofquist, Alan K.
A1 Baldwin, Albert S.
YR 1995
UL http://science.sciencemag.org/content/270/5234/283.abstract
AB 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.