PMID- 8776731
OWN - NLM
STAT- MEDLINE
DCOM- 19961230
LR  - 20220409
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 10
IP  - 6
DP  - 1996 Jun
TI  - Involvement of CCAAT/enhancer-binding protein and nuclear factor-kappa B binding 
      sites in interleukin-6 promoter inhibition by estrogens.
PG  - 713-22
AB  - Bone loss observed in postmenopausal women is clearly associated with a decrease 
      in estrogen levels. Interleukin 6 (IL-6), a multifunctional cytokine involved in 
      osteoclast differentiation, is secreted by osteoblasts and appears to be a key 
      molecule in the osteoporotic process. As previous reports have shown that the 
      human IL-6 promoter is inhibited by estradiol, we investigated the mechanism of 
      estradiol (E2)-mediated IL-6 inhibition in human cells. Analysis of the IL-6 
      secretion as a function of time in osteoblastoma Saos-2 cells, using an IL-6 
      ELISA test, showed that a maximal E2 inhibition of tumor necrosis factor-alpha 
      (TNF alpha) induction could be monitored between 2 and 24 h of treatment. IL-6 
      inhibition was clearly estrogen agonist-specific in Saos-2 and MCF7 cells. 
      Transient transfections of HeLa cells with a pIL-6/CAT plasmid and an estrogen 
      receptor (human ER) expression vector, confirmed the role of the human ER in 
      inhibition of the IL-6 promoter. Deletion and mutational analysis of the promoter 
      highlighted the role of the -185/-60 region and showed that in both MCF7 and HeLa 
      cells, the nuclear factor-IL 6 (NF-IL6) site cooperates with the nuclear 
      factor-kappa B (NF-kappa B) motif to produce maximal induction by TNF alpha, 
      whereas the CCAAT/enhancer-binding protein (C/EBP) site displayed different 
      cooperative effects toward NF-kappa B depending on the cell line used. In HeLa 
      cells, but not in MCF7 cells, we defined an essential role for the C/EBP site by 
      showing that the E2 sensitivity was clearly dependent on its integrity. In these 
      cell lines, the NF-kappa B site mutation abrogated both the TNF alpha-and E2- 
      sensitivity of the construct.
FAU - Galien, R
AU  - Galien R
AD  - Roussel Uclaf, Romainville, France.
FAU - Evans, H F
AU  - Evans HF
FAU - Garcia, T
AU  - Garcia T
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (CCAAT-Enhancer-Binding Proteins)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Interleukin-6)
RN  - 0 (NF-kappa B)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.3.1.28 (Chloramphenicol O-Acetyltransferase)
SB  - IM
MH  - Adenocarcinoma/drug therapy/pathology
MH  - Base Sequence
MH  - Binding Sites
MH  - Breast Neoplasms/drug therapy/pathology
MH  - CCAAT-Enhancer-Binding Proteins
MH  - Chloramphenicol O-Acetyltransferase/drug effects/genetics
MH  - DNA-Binding Proteins/metabolism
MH  - Estradiol/*metabolism/*pharmacology
MH  - Genes, Reporter
MH  - HeLa Cells
MH  - Humans
MH  - Interleukin-6/*antagonists & inhibitors/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - NF-kappa B/*metabolism
MH  - Nuclear Proteins/metabolism
MH  - Promoter Regions, Genetic
MH  - Receptors, Estrogen/antagonists & inhibitors/metabolism
MH  - Recombinant Fusion Proteins/drug effects/genetics
MH  - STAT3 Transcription Factor
MH  - Sequence Deletion
MH  - *Trans-Activators
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - Tumor Necrosis Factor-alpha/metabolism/pharmacology
EDAT- 1996/06/01 00:00
MHDA- 1996/06/01 00:01
CRDT- 1996/06/01 00:00
PHST- 1996/06/01 00:00 [pubmed]
PHST- 1996/06/01 00:01 [medline]
PHST- 1996/06/01 00:00 [entrez]
AID - 10.1210/mend.10.6.8776731 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1996 Jun;10(6):713-22. doi: 10.1210/mend.10.6.8776731.