Evidence map›Paper›PMID 25619261›Full record

ArticleClinical and experimental immunology2015

Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses.

M J Ashbrook, K L McDonough, J J Pituch, P L Christopherson, T T Cornell, D T Selewski, T P Shanley, N B Blatt

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

Article in Clinical and experimental immunology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.6field-weighted citation impact, top 10% 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

36 citing papers in PubMed, 55 citations in OpenAlex.

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  14. Engineering metabolism to modulate immunity.Advanced drug delivery reviews · 2024
    Review
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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

8 authors at 1 institution in 1 country.

M J AshbrookDivisions of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
K L McDonoughPediatric Critical Care, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
J J PituchDivisions of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
P L ChristophersonDivisions of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
T T CornellPediatric Critical Care, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
D T SelewskiDivisions of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
T P ShanleyPediatric Critical Care, Department of Pediatrics and Communicable Diseases, University of Michigan, Ann Arbor, MI, USA.
N B BlattDivisions of Pediatric Nephrology, University of Michigan, Ann Arbor, MI, USA.
University of Michigan–Ann Arbor · US

Funding

MKP-2 as an Endogenous Regulator of the Pro-Inflammatory Response in SepsisK08HD062142 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI CORNELL, TIMOTHY T · 2010 to 2013
$505k
Immune Dysregulation in UremiaK08DK093785 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI BLATT, NEAL B · 2012 to 2014
$460k
NICHD NIH HHS K08 HD062142NICHD NIH HHS K08HD062142NIDDK NIH HHS K08 DK093785NIDDK NIH HHS K08DK093785
6 · The paper itself

Abstract

Citrate, a central component of cellular metabolism, is a widely used anti-coagulant due to its ability to chelate calcium. Adenosine triphosphate (ATP)-citrate lyase, which metabolizes citrate, has been shown to be essential for inflammation, but the ability of exogenous citrate to impact inflammatory signalling cascades remains largely unknown. We hypothesized that citrate would modulate inflammatory responses as both a cellular metabolite and calcium chelator, and tested this hypothesis by determining how clinically relevant levels of citrate modulate monocyte proinflammatory responses to lipopolysaccharide (LPS) in a human acute monocytic leukaemia cell line (THP-1). In normal medium (0.4 mM calcium), citrate inhibited LPS-induced tumour necrosis factor (TNF)-α and interleukin (IL)-8 transcripts, whereas in medium supplemented with calcium (1.4 mM), TNF-α and IL-8 levels increased and appeared independent of calcium chelation. Using an IL-8-luciferase plasmid construct, the same increased response was observed in the activation of the IL-8 promoter region, suggesting transcriptional regulation. Tricarballylic acid, an inhibitor of ATP-citrate lyase, blocked the ability of citrate to augment TNF-α, linking citrate's augmentation effect with its metabolism by ATP-citrate lyase. In the presence of citrate, increased histone acetylation was observed in the TNF-α and IL-8 promoter regions of THP-1 cells. We observed that citrate can both augment and inhibit proinflammatory cytokine production via modulation of inflammatory gene transactivation. These findings suggest that citrate anti-coagulation may alter immune function through complex interactions with the inflammatory response.

Indexed as

AcetylationCalciumCell Line, TumorCitric AcidGene Expression RegulationHistonesHumansInflammationInterleukin-8LipopolysaccharidesMonocytesPromoter Regions, GeneticRNA, MessengerTranscriptional ActivationTumor Necrosis Factor-alphaCalciumCitric AcidHistonesInterleukin-8LipopolysaccharidesRNA, MessengerTumor Necrosis Factor-alphacitrateepigeneticsinflammationmonocytes

Identifiers

PMID25619261
PMCPMC4449780
OpenAlexW1884221296

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.