PMID- 7659084
OWN - NLM
STAT- MEDLINE
DCOM- 19951002
LR  - 20240109
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 9
IP  - 4
DP  - 1995 Apr
TI  - Negative cross-talk between RelA and the glucocorticoid receptor: a possible 
      mechanism for the antiinflammatory action of glucocorticoids.
PG  - 401-12
AB  - Glucocorticoids are efficient antiinflammatory agents, and their effects include 
      transcriptional repression of several cytokines and adhesion molecules. Whereas 
      glucocorticoids down-regulate the expression of genes relevant during 
      inflammation, nuclear factor (NF)-kappa B/Rel proteins function as important 
      positive regulators of these genes. The expression of intercellular adhesion 
      molecule-1 (ICAM-1), which plays an essential role in recruitment and migration 
      of leukocytes to sites of inflammation, is also down-regulated by 
      glucocorticoids. We found that a functional NF-kappa B site in the ICAM-1 
      promoter, which can be activated by either 12-O-tetradecanoylphorbol-13-acetate 
      or tumor necrosis factor-alpha (TNF alpha), is also the target for 
      glucocorticoids. In this report we present evidence that the ligand-activated 
      glucocorticoid receptor (GR) is able to repress RelA-mediated activation of the 
      ICAM-1 NF-kappa B site. Conversely, transcriptional activation by GR via a 
      glucocorticoid response element is specifically repressed by RelA, but not by 
      other NF-kappa B/Rel family members. Mutational analysis of GR demonstrates that 
      the DNA binding domain and the ligand binding domain are required for the 
      functional repression of NF-kappa B activation. Despite the importance of the DNA 
      binding domain, we found that the transcriptional repression of NF-kappa B, 
      mediated by GR, is not caused by binding of GR to the ICAM-1 NF-kappa B element, 
      but by a physical interaction between the GR and RelA protein. The repressive 
      effect of GR on NF-kappa B-mediated activation was not shared by other 
      steroid/thyroid receptors. Only the progesterone receptor, which belongs to the 
      same subfamily as GR and which possesses high homology with GR, was able to 
      repress NF-kappa B-mediated transcription. These studies highlight a possible 
      molecular mechanism that can explain the antiinflammatory effects of 
      glucocorticoid treatment during inflammation.
FAU - Caldenhoven, E
AU  - Caldenhoven E
AD  - Hubrecht Laboratory, Netherlands Institute for Developmental Biology, Utrecht.
FAU - Liden, J
AU  - Liden J
FAU - Wissink, S
AU  - Wissink S
FAU - Van de Stolpe, A
AU  - Van de Stolpe A
FAU - Raaijmakers, J
AU  - Raaijmakers J
FAU - Koenderman, L
AU  - Koenderman L
FAU - Okret, S
AU  - Okret S
FAU - Gustafsson, J A
AU  - Gustafsson JA
FAU - Van der Saag, P T
AU  - Van der Saag PT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Glucocorticoids)
RN  - 0 (NF-kappa B)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Receptors, Steroid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Steroids)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Base Sequence
MH  - Cell Line, Transformed
MH  - Cells, Cultured
MH  - Chlorocebus aethiops
MH  - Gene Expression Regulation/*drug effects
MH  - Glucocorticoids/*pharmacology
MH  - Humans
MH  - Intercellular Adhesion Molecule-1/biosynthesis/genetics
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - NF-kappa B/metabolism/*physiology
MH  - Promoter Regions, Genetic
MH  - Receptors, Glucocorticoid/drug effects/genetics/*physiology
MH  - Receptors, Steroid/metabolism
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Steroids
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factor RelA
MH  - Transcriptional Activation/drug effects
MH  - Tumor Necrosis Factor-alpha/pharmacology
EDAT- 1995/04/01 00:00
MHDA- 1995/04/01 00:01
CRDT- 1995/04/01 00:00
PHST- 1995/04/01 00:00 [pubmed]
PHST- 1995/04/01 00:01 [medline]
PHST- 1995/04/01 00:00 [entrez]
AID - 10.1210/mend.9.4.7659084 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1995 Apr;9(4):401-12. doi: 10.1210/mend.9.4.7659084.