Estrogen receptor inhibits interleukin-6 gene expression by disruption of nuclear factor kappaB transactivation.
The estrogen receptor (ER) suppresses interleukin-6 (IL-6) gene expression through interaction with nuclear factor kappaB (NF-kappaB) in a hormone-dependent manner. Classic ER binding to DNA is not required and the mechanism of repression is unclear. Previously reported studies suggest that the interference of NF-kappaB binding to DNA by ER may play an important role. An alternative model for repression would be the disruption of NF-kappaB transactivation. In the present study, gel shift assays were used to examine the binding of RelA and p50 dimers to the IL-6 promoter in the presence of ER. The effect of ER on NF-kappaB transactivation was studied independent of NF-kappaB binding to DNA using the mammalian one-hybrid system. ER had little effect on the binding of homodimers or heterodimers of RelA and p50 to the IL-6 promoter. In transfection experiments, both ERalpha and ERbeta inhibited NF-kappaB-mediated expression in a hormone dependent manner with repression also dependent upon dimerization of RelA with p50. Mutant ER that is unable to transactivate failed to repress NF-kappaB expression, but deletion of the N-terminal portion of the receptor had no effect. Taken together, these results suggest that the disruption of NF-kappaB-mediated transactivation plays a significant role in ER inhibition of IL-6 gene expression.
Liu
Hui
H
Department of Geriatrics, Donald W. Reynolds Center on Aging, The University of Arkansas for Medical Sciences and the Geriatric Research, Education and Clinical Center, Central Arkansas Veterans Healthcare System, Little Rock, AR 72205, USA.
Liu
Kenian
K
Bodenner
Donald L
DL
D001483:Base Sequence; D017931:DNA Primers; D005786:Gene Expression Regulation / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
D017931:DNA Primers; D015850:Interleukin-6; D016328:NF-kappa B; D009687:Nuclear Proteins; D011960:Receptors, Estrogen