I kappaB alpha-independent downregulation of NF-kappaB activity by glucocorticoid receptor.
EMBO J
; 16(15): 4698-707, 1997 Aug 01.
Article
in En
| MEDLINE
| ID: mdl-9303314
ABSTRACT
I kappaB alpha is an inhibitor protein that prevents nuclear transport-and activation of the transcription factor NF-kappaB. In acute inflammation, NF-kappaB is activated and increases the expression of several pro-inflammatory cytokine and chemokine genes. Glucocorticoids counteract this process. It has been proposed that the glucocorticoid-dependent inhibition of NF-kappaB activity is mediated by increased synthesis of I kappaB alpha which should then sequester NF-kappaB in an inactive cytoplasmic form. Here, we show by the use of a mutant glucocorticoid receptor and steroidal ligands that hormone-induced I kappaB alpha synthesis and inhibition of NF-kappaB activity are separable biochemical processes. A dimerization-defective glucocorticoid receptor mutant that does not enhance the I kappaB alpha level is still able to repress NF-kappaB activity. Conversely, glucocorticoid analogues competent in enhancing I kappaB alpha synthesis do not repress NF-kappaB activity. These results demonstrate that increased synthesis of I kappaB alpha is neither required nor sufficient for the hormone-mediated downmodulation of NF-kappaB activity.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Receptors, Glucocorticoid
/
NF-kappa B
/
I-kappa B Proteins
/
DNA-Binding Proteins
Limits:
Animals
/
Humans
Language:
En
Journal:
EMBO J
Year:
1997
Document type:
Article
Affiliation country:
Germany