ROLE OF TRANSCRIPTIONAL ACTIVATION OF I-KAPPA-B-ALPHA IN MEDIATION OF IMMUNOSUPPRESSION BY GLUCOCORTICOIDS

被引:1446
作者
SCHEINMAN, RI
COGSWELL, PC
LOFQUIST, AK
BALDWIN, AS
机构
[1] UNIV N CAROLINA, LINEBERGER COMPREHENS CANC CTR, CHAPEL HILL, NC 27599 USA
[2] UNIV N CAROLINA, DEPT BIOL, CHAPEL HILL, NC 27599 USA
关键词
D O I
10.1126/science.270.5234.283
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
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页码:283 / 286
页数:4
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