Evidence map›Paper›PMID 27381163›Full record

ArticleNature communications2016

Signal transduction controls heterogeneous NF-κB dynamics and target gene expression through cytokine-specific refractory states.

Antony Adamson, Christopher Boddington, Polly Downton, William Rowe, James Bagnall, Connie Lam, Apolinar Maya-Mendoza, Lorraine Schmidt, Claire V Harper, David G Spiller and 4 more

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed
4.6field-weighted citation impact, top 5% 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

59 citing papers in PubMed, 86 citations in OpenAlex.

  1. Trial
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  7. Autonomous Oscillations of NF-κB.Advances in experimental medicine and biology · 2026
    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

14 authors at 3 institutions in 2 countries.

Antony AdamsonSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Christopher BoddingtonSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Polly DowntonSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.ORCID 0000-0002-1617-6153
William RoweSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
James BagnallSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Connie LamSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Apolinar Maya-MendozaThe Danish Cancer Society Research Center, Strandboulevarden 49, DK-2100 Copenhagen, Denmark.
Lorraine SchmidtSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Claire V HarperSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
David G SpillerSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
David A RandWarwick Systems Biology and Mathematics Institute, University of Warwick, Coventry CV4 7AL, UK.
Dean A JacksonSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Michael R H WhiteSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
Pawel PaszekSystems Microscopy Centre, Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK.ORCID 0000-0002-0363-0716
University of Manchester · GBDanish Cancer Society · DKUniversity of Warwick · GB

Funding

Biotechnology and Biological Sciences Research Council BB/F00561X/1Biotechnology and Biological Sciences Research Council BB/F005938/1Biotechnology and Biological Sciences Research Council BB/I017976/1Biotechnology and Biological Sciences Research Council BB/K003097/1Medical Research Council G0500346Medical Research Council MR/K015885/1Medical Research Council MR/M008908/1Wellcome Trust
6 · The paper itself

Abstract

Cells respond dynamically to pulsatile cytokine stimulation. Here we report that single, or well-spaced pulses of TNFα (>100 min apart) give a high probability of NF-κB activation. However, fewer cells respond to shorter pulse intervals (<100 min) suggesting a heterogeneous refractory state. This refractory state is established in the signal transduction network downstream of TNFR and upstream of IKK, and depends on the level of the NF-κB system negative feedback protein A20. If a second pulse within the refractory phase is IL-1β instead of TNFα, all of the cells respond. This suggests a mechanism by which two cytokines can synergistically activate an inflammatory response. Gene expression analyses show strong correlation between the cellular dynamic response and NF-κB-dependent target gene activation. These data suggest that refractory states in the NF-κB system constitute an inherent design motif of the inflammatory response and we suggest that this may avoid harmful homogenous cellular activation.

Indexed as

Cell Line, TumorFeedback, PhysiologicalGene Expression RegulationGenes, ReporterGreen Fluorescent ProteinsHumansI-kappa B KinaseInterleukin-1betaLuminescent ProteinsNeuronsNF-kappa BNF-KappaB Inhibitor alphaReceptors, Tumor Necrosis Factor, Type IRecombinant Fusion ProteinsRed Fluorescent ProteinRNA, Small Interferingenhanced green fluorescent proteinGreen Fluorescent ProteinsI-kappa B KinaseIL1B protein, humanInterleukin-1betaLuminescent ProteinsNF-kappa BNF-KappaB Inhibitor alphaReceptors, Tumor Necrosis Factor, Type IRecombinant Fusion ProteinsRed Fluorescent ProteinRNA, Small InterferingTNFAIP3 protein, humanTumor Necrosis Factor-alphaTumor Necrosis Factor alpha-Induced Protein 3

Identifiers

PMID27381163
PMCPMC4935804
OpenAlexW2465275830

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.