Evidence map›Paper›PMID 24530961›Full record

ArticleAtherosclerosis2014

Effect of low extracellular pH on NF-κB activation in macrophages.

A B Gerry, D S Leake

Abstract readComparative Study
In one paragraph

Article in Atherosclerosis, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Function and contribution of two putativeInfection and immunity · 2024
    Article
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  7. Article
  8. Article
  9. Article
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  13. Review
  14. Article
  15. The function of cathepsins B, D, and X in atherosclerosis.American journal of cardiovascular disease · 2016
    Article
  16. Metabolic Connection of Inflammatory Pain: Pivotal Role of a Pyruvate Dehydrogenase Kinase-Pyruvate Dehydrogenase-Lactic Acid Axis.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015
    Article
  17. Review
  18. Review
  19. Article
  20. Article
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

2 authors.

A B GerryInstitute of Cardiovascular and Metabolic Research, School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights, Reading, Berkshire RG6 6UB, United Kingdom. Electronic address: Andrew.Gerry@adaptimmune.com.
D S LeakeInstitute of Cardiovascular and Metabolic Research, School of Biological Sciences, Hopkins Building, University of Reading, Whiteknights, Reading, Berkshire RG6 6UB, United Kingdom. Electronic address: d.s.leake@reading.ac.uk.

Funding

Biotechnology and Biological Sciences Research CouncilBritish Heart Foundation PG/04/015/16658
6 · The paper itself

Abstract

objectiveMany diseases, including atherosclerosis, involve chronic inflammation. The master transcription factor for inflammation is NF-κB. Inflammatory sites have a low extracellular pH. Our objective was to demonstrate the effect of pH on NF-κB activation and cytokine secretion.

methodsMouse J774 macrophages or human THP-1 or monocyte-derived macrophages were incubated at pH 7.0-7.4 and inflammatory cytokine secretion and NF-κB activity were measured.

resultsA pH of 7.0 greatly decreased pro-inflammatory cytokine secretion (TNF or IL-6) by J774 macrophages, but not THP-1 or human monocyte-derived macrophages. Upon stimulation of mouse macrophages, the levels of IκBα, which inhibits NF-κB, fell but low pH prevented its later increase, which normally restores the baseline activity of NF-κB, even though the levels of mRNA for IκBα were increased. pH 7.0 greatly increased and prolonged NF-κB binding to its consensus promoter sequence, especially the anti-inflammatory p50:p50 homodimers. Human p50 was overexpressed using adenovirus in THP-1 macrophages and monocyte-derived macrophages to see if it would confer pH sensitivity to NF-κB activity in human cells. Overexpression of p50 increased p50:p50 DNA-binding and in THP-1 macrophages inhibited considerably TNF and IL-6 secretion, but there was still no effect of pH on p50:p50 DNA binding or cytokine secretion.

conclusionA modest decrease in pH can sometimes have marked effects on NF-κB activation and cytokine secretion and might be one reason to explain why mice normally develop less atherosclerosis than do humans.

Indexed as

Hydrogen-Ion ConcentrationAnimalsAtherosclerosisCell LineCells, CulturedConsensus SequenceDisease SusceptibilityDNAExtracellular FluidHumansI-kappa B ProteinsInterleukin-6MacrophagesMiceMonocytesNF-kappa BDNAI-kappa B ProteinsIL6 protein, humanInterleukin-6interleukin-6, mouseNF-kappa BNF-KappaB Inhibitor alphaNF-kappa B p50 SubunitNFKBIA protein, humanNfkbia protein, mouseRecombinant Fusion ProteinsTumor Necrosis Factor-alphaAtherosclerosisCytokinesInflammationLow pHMacrophagesNF-κBp50 Homodimers

Identifiers

PMID24530961
PMCPMC3989994

What OpenQuestion holds

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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.