Role of transcriptional activation of I kappa B alpha in mediation of immunosuppression by glucocorticoids.
Science
; 270(5234): 283-6, 1995 Oct 13.
Article
en En
| MEDLINE
| ID: mdl-7569975
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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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Dexametasona
/
FN-kappa B
/
Terapia de Inmunosupresión
/
Proteínas I-kappa B
/
Proteínas de Unión al ADN
/
Inmunosupresores
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
1995
Tipo del documento:
Article
País de afiliación:
Estados Unidos
Pais de publicación:
Estados Unidos