PMID- 10614622
OWN - NLM
STAT- MEDLINE
DCOM- 20000113
LR  - 20061115
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 141
IP  - 1
DP  - 2000 Jan
TI  - Molecular analysis of the inhibition of monocyte chemoattractant protein-1 gene 
      expression by estrogens and xenoestrogens in MCF-7 cells.
PG  - 50-9
AB  - Xenoestrogens (XEs) are a diverse group of chemicals that mimic estrogenic 
      actions and may have adverse effects on human health. The influence of these 
      compounds on cytokine production or immune system function remains unclear. In 
      this study we have examined the effects of 17beta-estradiol (E2) and XEs on 
      chemoattractant cytokine (chemokine) production and analyzed the molecular 
      mechanism. Monocyte chemoattractant protein-1 (MCP-1), also termed monocyte 
      chemotactic and activating factor, is a member of the chemokine family and 
      attracts mainly blood monocytes. Human mammary tumor cell line MCF-7 cells 
      produce a large quantity of MCP-1 in response to interleukin-1alpha (IL-1alpha). 
      Addition of E2 to MCF-7 cells inhibited MCP-1 production in a dose-dependent 
      manner. XEs, bisphenol A, and NP also inhibited MCP-1 production, although the 
      potency was 3-4 orders of magnitude lower than that of E2. E2, bisphenol A, and 
      NP inhibited MCP-1 messenger RNA expression in MCF-7 cells. Two closely located 
      nuclear factor-kappaB sites, A1 and A2, have been identified in the promoter of 
      the human MCP-1 gene. A luciferase construct containing this enhancer region 
      (pGLM-ENH) was activated by IL-1alpha, and a mutation at either the A1 or A2 site 
      resulted in a loss of IL-1alpha responsiveness. Treatment with E2 or XEs 
      decreased the IL-1alpha-inducible pGLM-ENH luciferase activity significantly. In 
      an electrophoretic mobility shift assay and supershift analysis, we found that 
      treatment with E2 or XEs diminished the IL-1alpha-induced complex formation with 
      both A1 and A2 probes, which was identified immunochemically to consist of 
      nuclear factor-kappaB, p50, and p65. The IL-1alpha-induced p50/c-Rel complex to 
      the A2 probe was also, to a lesser extent, decreased by E2 or XE treatment. The 
      effects of E2 and XEs on the expression of MCP-1 seem to be much more dramatic 
      than the effects of these agents on the promoters used in the luciferase assay, 
      suggesting the involvement of an additional site(s) of the promoter region of the 
      MCP-1 gene or posttranscriptional regulation of MCP-1 gene expression by E2 and 
      XEs. This work represents the first report describing possible regulation of 
      immune system function by XEs through inhibiting chemokine production.
FAU - Inadera, H
AU  - Inadera H
AD  - Department of Molecular Preventive Medicine, University of Tokyo, School of 
      Medicine, Japan.
FAU - Sekiya, T
AU  - Sekiya T
FAU - Yoshimura, T
AU  - Yoshimura T
FAU - Matsushima, K
AU  - Matsushima K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Chemokine CCL2)
RN  - 0 (Estradiol Congeners)
RN  - 0 (Estrogens)
RN  - 0 (Interleukin-1)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (Recombinant Proteins)
RN  - EC 1.13.12.- (Luciferases)
SB  - IM
MH  - Blotting, Northern
MH  - Cell Line
MH  - Chemokine CCL2/*biosynthesis/genetics
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Estradiol Congeners/*pharmacology
MH  - Estrogens/*pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Humans
MH  - Interleukin-1/biosynthesis
MH  - Luciferases/metabolism
MH  - NF-kappa B/biosynthesis/genetics
MH  - Plasmids
MH  - RNA, Messenger/biosynthesis
MH  - Recombinant Proteins/pharmacology
MH  - Transfection
EDAT- 1999/12/30 00:00
MHDA- 1999/12/30 00:01
CRDT- 1999/12/30 00:00
PHST- 1999/12/30 00:00 [pubmed]
PHST- 1999/12/30 00:01 [medline]
PHST- 1999/12/30 00:00 [entrez]
AID - 10.1210/endo.141.1.7233 [doi]
PST - ppublish
SO  - Endocrinology. 2000 Jan;141(1):50-9. doi: 10.1210/endo.141.1.7233.