Evidence map›Paper›PMID 26843329›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2016

GAPDH Binding to TNF-α mRNA Contributes to Posttranscriptional Repression in Monocytes: A Novel Mechanism of Communication between Inflammation and Metabolism.

Patrick Millet, Vidula Vachharajani, Linda McPhail, Barbara Yoza, Charles E McCall

Open access · greenAbstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.

0numbers the graph read from it
0cells of the map it votes in
75citing papers in PubMed
5.8field-weighted citation impact, top 4% 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

75 citing papers in PubMed, 133 citations in OpenAlex.

  1. Review
  2. Review
  3. MAIT cell plasticity generates CD4Cellular & molecular immunology · 2026
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  6. Effect of PKM2 onFrontiers in cellular and infection microbiology · 2026
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  15. Article
  16. Review
  17. Review
  18. Article
  19. Article
  20. Review

15 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

5 authors at 1 institution in 1 country.

Patrick MilletMolecular Genetics and Genomics Program, Wake Forest University School of Medicine, Winston-Salem, NC 27157;
Vidula VachharajaniDepartment of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157; Department of Anesthesiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157;ORCID http://orcid.org/0000-0002-0892-7084
Linda McPhailDepartment of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157; and.
Barbara YozaDepartment of General Surgery, Wake Forest University School of Medicine, Winston-Salem, NC 27157.
Charles E McCallDepartment of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, NC 27157; Chmccall@wfubmc.edu.ORCID http://orcid.org/0000-0002-9082-469X
Wake Forest 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
Bioenergetic and Epigenetic Reprogramming by Obesity in SepsisR01GM099807 · NIGMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI VACHHARAJANI, VIDULA · 2012 to 2020
$3.1M
Epigenetics of Severe Systemic InflammationR01AI079144 · NIAID · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MCCALL, CHARLES EMORY · 2010 to 2014
$2.0M
Mitochondrial Biogenesis is Regulated by RelB During InflammationR01GM102497 · NIGMS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI MCCALL, CHARLES EMORY · 2014 to 2017
$1.2M
NIAID NIH HHS R01 AI065791NIAID NIH HHS R01AI065791NIAID NIH HHS R01 AI079144NIAID NIH HHS R01AI079144NIGMS NIH HHS R01 GM099807NIGMS NIH HHS R01GM099807NIGMS NIH HHS R01 GM102497NIGMS NIH HHS R01GM102497
6 · The paper itself

Abstract

Expression of the inflammatory cytokine TNF is tightly controlled. During endotoxin tolerance, transcription of TNF mRNA is repressed, although not entirely eliminated. Production of TNF cytokine, however, is further controlled by posttranscriptional regulation. In this study, we detail a mechanism of posttranscriptional repression of TNF mRNA by GAPDH binding to the TNF 3' untranslated region. Using RNA immunoprecipitation, we demonstrate that GAPDH-TNF mRNA binding increases when THP-1 monocytes are in a low glycolysis state, and that this binding can be reversed by knocking down GAPDH expression or by increasing glycolysis. We show that reducing glycolysis decreases TNF mRNA association with polysomes. We demonstrate that GAPDH-TNF mRNA binding results in posttranscriptional repression of TNF and that the TNF mRNA 3' untranslated region is sufficient for repression. Finally, after exploring this model in THP-1 cells, we demonstrate this mechanism affects TNF expression in primary human monocytes and macrophages. We conclude that GAPDH-TNF mRNA binding regulates expression of TNF based on cellular metabolic state. We think this mechanism has potentially significant implications for treatment of various immunometabolic conditions, including immune paralysis during septic shock.

Indexed as

Blotting, WesternEnzyme-Linked Immunosorbent AssayGene Expression RegulationGene Knockdown TechniquesGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)GlycolysisHumansImmunoprecipitationInflammationMonocytesReal-Time Polymerase Chain ReactionRNA, MessengerRNA Processing, Post-TranscriptionalRNA, Small InterferingTransfectionTumor Necrosis Factor-alphaGlyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)RNA, MessengerRNA, Small InterferingTumor Necrosis Factor-alpha

Identifiers

PMID26843329
PMCPMC4779706
OpenAlexW2266391474

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.