Evidence map›Paper›PMID 28877759›Full record

ArticleBiology of sex differences2017

The effects of 17 alpha-estradiol to inhibit inflammation in vitro.

Roberta S Santos, Luciana A de Fatima, Aaron P Frank, Everardo M Carneiro, Deborah J Clegg

Open access · goldAbstract read
In one paragraph

Article in Biology of sex differences, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.2field-weighted citation impact, top 6% 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

28 citing papers in PubMed, 45 citations in OpenAlex.

  1. Polymorphism in the Promoter Region of theFrontiers in immunology · 2020
    Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. 17-α-Estradiol Has Sex-Specific Effects on Neuroinflammation That Are Partly Reversed by Gonadectomy.The journals of gerontology. Series A, Biological sciences and medical sciences · 2022
    Article
  7. Article
  8. Review
  9. Estrogen Suppresses Cytokines Release in cc4821Frontiers in microbiology · 2022
    Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Effects of 17β-Estradiol on Monocyte/Macrophage Response toFrontiers in cellular and infection microbiology · 2021
    Article
  17. Article
  18. Article
  19. Review
  20. Review
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

5 authors at 2 institutions in 2 countries.

Roberta S SantosBiomedical Sciences Dept, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Luciana A de FatimaBiomedical Sciences Dept, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Aaron P FrankBiomedical Sciences Dept, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA.
Everardo M CarneiroObesity and Comorbidities Research Center (OCRC), Institute of Biology, State University of Campinas-UNICAMP, Campinas, SP, Brazil.
Deborah J CleggBiomedical Sciences Dept, Diabetes and Obesity Research Division, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Los Angeles, CA, 90048, USA. deborah.clegg@cshs.org.
Cedars-Sinai Medical Center · USUniversidade Estadual de Campinas (UNICAMP) · BR

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

background17 Alpha-estradiol (17 α-E2) is a natural, non-feminizing stereoisomer of 17 beta-estradiol (17 β-E2). Whereas much is known about the physiological effects of 17 β-E2, much less is known about 17 α-E2. For example, 17 β-E2 exerts anti-inflammatory effects in neurons and adipocytes through binding and activation of estrogen receptor alpha (ERα); however, if 17 α-E2 has similar effects on inflammation is currently unknown.

methodsTo begin to address this, we analyzed the ability of 17 α-E2 and 17 β-E2 to suppress lipopolysaccharide (LPS)-induced inflammation in vitro using embryonic fibroblast cells (MEF) from wild type and total body ERα (ERKO) male and female mice. Additionally, we further probed if there were sex differences with respect to the effects of E2s using primary pre-adipocyte cells from C57BL/6J male and female mice. Also, we probed mechanistically the effects of E2s in fully differentiated 3T3-L1 cells.

resultsBoth E2s decreased LPS-induced markers of inflammation Tnf-α and Il-6, and increased the anti-inflammatory markers Il-4 and IL-6 receptor (Il-6ra) in MEF cells. To begin to understand the mechanisms by which both E2's mediate their anti-inflammatory effects, we probed the role of ERα using two methods. First, we used MEF cells from ERKO mice and found reductions in ERα diminished the ability of 17 α-E2 to suppress Tnf-α in female but not in male cells, demonstrating a sexual dimorphism in regard to the role of ERα to mediate 17 α-E2's effects. Second, we selectively reduced the expression of ERα in 3T3-L1 cells using siRNA and found reductions in ERα diminished the ability of both E2s to suppress Tnf-α and Il-6 expression. Lastly, to determine the mechanisms by which E2s reduce inflammation, we explored the role of NFκB-p65 and found both E2s decreased NFκB-p65 expression.

conclusionsIn conclusion, we demonstrate for the first time that 17 α-E2, as well as 17 β-E2, suppresses inflammation through their effects on ERα and NFκB-p65.

Indexed as

3T3-L1 CellsAdipocytesAnimalsAnti-Inflammatory Agents, Non-SteroidalEstradiolEstrogen Receptor alphaFemaleFibroblastsInflammationLipopolysaccharidesMaleMiceMice, Inbred C57BLMice, KnockoutSex CharacteristicsTranscription Factor RelAAnti-Inflammatory Agents, Non-SteroidalEstradiolEstrogen Receptor alphaLipopolysaccharidesRela protein, mouseTranscription Factor RelA17 Alpha-estradiol (17 α-E2)17 Beta-estradiol (17 β-E2)Cell cultureInflammationSexual dimorphism

Identifiers

PMID28877759
PMCPMC5586055
OpenAlexW2753813909

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.