Evidence map›Paper›PMID 20351193›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2010

Estradiol suppresses NF-kappa B activation through coordinated regulation of let-7a and miR-125b in primary human macrophages.

Amy J Murphy, Paul M Guyre, Patricia A Pioli

Open access · bronzeAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 131 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 1 synthesis or guideline pooled it, 246 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Effect of Estrogen on Sirt1 Signaling in Human Macrophages.International journal of molecular sciences · 2025
    Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. The Role of Estrogen in Brain MicroRNAs Regulation.Advanced pharmaceutical bulletin · 2024
    Review
  14. Review
  15. Review
  16. Article
  17. Article
  18. Review
  19. Review
  20. Article

71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 2 countries.

Amy J MurphyDepartment of Physiology, Dartmouth Medical School, Lebanon, NH 03756, USA.
Paul M Guyre
Patricia A Pioli
Czech Academy of Sciences, Institute of Physiology · CZDartmouth College · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
VASCULAR LEUKOCYTES: BASIC IMMUNOBIOLOGY AND FUNCTIONAL PLASTICITYP20RR016437 · NCRR · DARTMOUTH COLLEGE · PI GREEN, WILLIAM R · 2001 to 2010
$24.3M
Glucocorticoid/cytokine mechanisms in endotoxemia.R01AI051547 · NIAID · DARTMOUTH COLLEGE · PI GUYRE, PAUL · 2003 to 2007
$1.9M
AUTOIMMUNITY &CONNECTIVE TISSUE BIOLOGY TRAININGT32AR007576 · NIAMS · DARTMOUTH COLLEGE · PI RIGBY, WILLIAM FREDERICK CARSON · 1994 to 2008
$1.7M
NCI NIH HHS P30 CA023108NCRR NIH HHS P20 RR 016437NCRR NIH HHS P20 RR016437NIAID NIH HHS R01 AI051547NIAID NIH HHS R01AI051547NIAMS NIH HHS T32 AR007576NIAMS NIH HHS T32AR007576
6 · The paper itself

Abstract

Previous findings suggest that 17beta-estradiol (estradiol) has a suppressive effect on TNF-alpha, but the mechanism by which estradiol regulates TNF-alpha expression in primary human macrophages is unknown. In this article, we demonstrate that pretreatment of human macrophages with estradiol attenuates LPS-induced TNF-alpha expression through the suppression of NF-kappaB activation. Furthermore, we show that activation of macrophages with LPS decreases the expression of kappaB-Ras2, an inhibitor of NF-kappaB signaling. Estradiol pretreatment abrogates this decrease, leading to the enhanced expression of kappaB-Ras2 with LPS stimulation. Additionally, we identified two microRNAs, let-7a and miR-125b, which target the kappaB-Ras2 3' untranslated region (UTR). LPS induces let-7a and inhibits miR-125b expression in human macrophages, and pretreatment with estradiol abrogates these effects. 3'UTR reporter assays demonstrate that let-7a destabilizes the kappaB-Ras2 3'UTR, whereas miR-125b enhances its stability, resulting in decreased kappaB-Ras2 in response to LPS. Our data suggest that pretreatment with estradiol reverses this effect. We propose a novel mechanism for estradiol inhibition of LPS-induced NF-kappaB signaling in which kappaB-Ras2 expression is induced by estradiol via regulation of let-7a and miR-125b. These findings are significant in that they are the first to demonstrate that estradiol represses NF-kappaB activation through the induction of kappaB-Ras2, a key inhibitor of NF-kappaB signaling.

Indexed as

3' Untranslated RegionsAnimalsCell LineCells, CulturedDown-RegulationEstradiolFemaleGene Expression RegulationHumansI-kappa B ProteinsLipopolysaccharidesMacrophagesMiceMicroRNAsNF-kappa Bras Proteins3' Untranslated RegionsEstradiolI-kappa B ProteinsLipopolysaccharidesMicroRNAsMIRN125 microRNA, humanmirnlet7 microRNA, humanNF-kappa Bras ProteinsRNA, MessengerTumor Necrosis Factor-alpha

Identifiers

PMID20351193
PMCPMC2882792
OpenAlexW1703103639

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.