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.
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
AUPHAN, N
DIDONATO, JA
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
DIDONATO, JA
ROSETTE, C
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
ROSETTE, C
HELMBERG, A
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
HELMBERG, A
KARIN, M
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
机构:
UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
AUPHAN, N
DIDONATO, JA
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UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
DIDONATO, JA
ROSETTE, C
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机构:
UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
ROSETTE, C
HELMBERG, A
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA
HELMBERG, A
KARIN, M
论文数: 0引用数: 0
h-index: 0
机构:
UNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USAUNIV CALIF SAN DIEGO, SCH MED,CTR GENET MOLEC,DEPT PHARMACOL, PROGRAM BIOMED SCI, LA JOLLA, CA 92093 USA