Evidence map›Paper›PMID 21562054›Full record

ArticleJournal of leukocyte biology2011

MicroRNA-146a regulates both transcription silencing and translation disruption of TNF-α during TLR4-induced gene reprogramming.

Mohamed El Gazzar, Ashley Church, Tiefu Liu, Charles E McCall

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of leukocyte biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
81citing papers in PubMed, 6 pooled it
3.6field-weighted citation impact, top 7% 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

81 citing papers in PubMed, 6 syntheses or guidelines pooled it, 129 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Association Between Single-Nucleotide Polymorphism (SNP) in miR-146a, miR-196a2, and miR-499 and Risk of Ischemic Stroke: A Meta-Analysis.Medical science monitor : international medical journal of experimental and clinical research · 2015
    Pooled it
  6. Pooled it
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Review
  20. Review

21 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

4 authors at 2 institutions in 1 country.

Mohamed El GazzarDepartment of Internal Medicine, East Tennessee State University College of Medicine, Johnson City, TN 37614, USA. elgazzar@etsu.edu
Ashley Church
Tiefu Liu
Charles E McCall
Wake Forest University · USEast Tennessee State University · US

Funding

NF-kB and Chromatin Changes in Human SepsisR01AI065791 · NIAID · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MCCALL, CHARLES EMORY · 2006 to 2015
$4.3M
Epigenetics of Severe Systemic InflammationR01AI079144 · NIAID · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MCCALL, CHARLES EMORY · 2010 to 2014
$2.0M
NIAID NIH HHS R01 AI065791NIAID NIH HHS R01AI-065791NIAID NIH HHS R01 AI079144NIAID NIH HHS R01AI-079144
6 · The paper itself

Abstract

Following the TLR-dependent initiation phase of acute systemic proinflammatory responses such as sepsis, an adaptive phase represses or activates a specific pattern of gene expression until the inflammation resolves. Here, we used the THP-1 sepsis cell model of bacterial LPS/endotoxin tolerance to show that TLR4-induced miR-146a supports the feed-forward adaptive processes that silence transcription and disrupt translation of acute proinflammatory genes. First, we found that miR-146a regulates a pathway that promotes the binding of transcription repressor RelB to the TNF-α promoter, a step known to precede histone and DNA modifications, which generate facultative heterochromatin to silence acute proinflammatory genes. However, once RelB binding occurred, miR-146a inhibition could not reverse compacted chromatin, and endotoxin tolerance persisted. Second, we observed that miR-146a regulates a pathway that supports assembly of the translation repressor complex of TNF-α by preventing the interaction of the RNA-binding protein effector Ago2 and RBM4. We also determined that once endotoxin tolerance is established, and specific genes have been reprogrammed, transcription and translation disruption can be reversed only by simultaneously depleting RelB and inhibiting miR-146a. Thus, miR-146a induction supports the TLR4-dependent shift from initiation to gene-specific repression at two levels. Our results also imply that therapies designed to reverse endotoxin tolerance as potential therapies for sepsis should be directed at the transcription and translation pathways of reprogramming.

Indexed as

Gene SilencingTranscription, GeneticBlotting, WesternChromatin ImmunoprecipitationEndotoxinsEnzyme-Linked Immunosorbent AssayHeterochromatinHistonesHumansImmune ToleranceImmunoprecipitationLipopolysaccharidesMacrophagesMicroRNAsPromoter Regions, GeneticReverse Transcriptase Polymerase Chain ReactionEndotoxinsHeterochromatinHistonesLipopolysaccharidesMicroRNAsMIRN146 microRNA, humanRBM4 protein, humanRELB protein, humanRNA-Binding ProteinsRNA, MessengerTLR4 protein, humanToll-Like Receptor 4Transcription Factor RelBTumor Necrosis Factor-alpha

Identifiers

PMID21562054
PMCPMC3157899
OpenAlexW2101317956

What OpenQuestion holds

Textmetadata
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.