Evidence map›Paper›PMID 27597652›Full record

ArticleAnnals of the rheumatic diseases2017

Treatment of inflammatory arthritis via targeting of tristetraprolin, a master regulator of pro-inflammatory gene expression.

E A Ross, A J Naylor, J D O'Neil, T Crowley, M L Ridley, J Crowe, T Smallie, T J Tang, J D Turner, L V Norling and 9 more

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

Article in Annals of the rheumatic diseases, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
5.4field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 73 citations in OpenAlex.

  1. Article
  2. Review
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  4. Article
  5. The EGR1/ZFP36 axis governs glycosphingolipid metabolic reprogramming in monocyte-derived macrophages in guillain-barré syndrome.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Article
  6. Review
  7. Article
  8. Review
  9. Post-transcriptional checkpoints in autoimmunity.Nature reviews. Rheumatology · 2023
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. Article
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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors at 8 institutions in 4 countries.

E A RossInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.
A J NaylorInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
J D O'NeilInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
T CrowleyInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
M L RidleyInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
J CroweKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
T SmallieInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
T J TangInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
J D TurnerInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
L V NorlingWilliam Harvey Research Institute, QMUL, London, UK.
S DominguezDivision of Rheumatology, Northwestern University, Chicago, Illinois, USA.
H PerlmanDivision of Rheumatology, Northwestern University, Chicago, Illinois, USA.
N M VerrillsSchool of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, New South Wales, Australia.
G KolliasDivision of Immunology, Biomedical Sciences Research Center 'Alexander Fleming', Vari, Greece.
M P VitekCognosci Inc., Research Triangle Park, North Carolina, USA.
A FilerInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
C D BuckleyInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
J L DeanKennedy Institute of Rheumatology, University of Oxford, Oxford, UK.
A R ClarkInstitute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
University of Birmingham · GBNorthwestern University · USUniversity of Oxford · GBAlexander Fleming Biomedical Sciences Research Center · GRCognosci (United States) · USUniversity of Glasgow · GBUniversity of Newcastle Australia · AUWilliam Harvey Research Institute · GB

Funding

Macrophage Modulation of Lung FibrosisR01HL134375 · NHLBI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PERLMAN, HARRIS R · 2017 to 2020
$2.9M
Development of a Novel RA/Atherosclerosis Mouse ModelR01AR064546 · NIAMS · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PERLMAN, HARRIS R · 2013 to 2017
$1.6M
Arthritis Research UK 19791Medical Research Council G0800207Medical Research Council G9818340NHLBI NIH HHS R01 HL134375NIAMS NIH HHS R01 AR064546Versus Arthritis 19614
6 · The paper itself

Abstract

objectivesTristetraprolin (TTP), a negative regulator of many pro-inflammatory genes, is strongly expressed in rheumatoid synovial cells. The mitogen-activated protein kinase (MAPK) p38 pathway mediates the inactivation of TTP via phosphorylation of two serine residues. We wished to test the hypothesis that these phosphorylations contribute to the development of inflammatory arthritis, and that, conversely, joint inflammation may be inhibited by promoting the dephosphorylation and activation of TTP.

methodsThe expression of TTP and its relationship with MAPK p38 activity were examined in non-inflamed and rheumatoid arthritis (RA) synovial tissue. Experimental arthritis was induced in a genetically modified mouse strain, in which endogenous TTP cannot be phosphorylated and inactivated. In vitro and in vivo experiments were performed to test anti-inflammatory effects of compounds that activate the protein phosphatase 2A (PP2A) and promote dephosphorylation of TTP.

resultsTTP expression was significantly higher in RA than non-inflamed synovium, detected in macrophages, vascular endothelial cells and some fibroblasts and co-localised with MAPK p38 activation. Substitution of TTP phosphorylation sites conferred dramatic protection against inflammatory arthritis in mice. Two distinct PP2A agonists also reduced inflammation and prevented bone erosion. In vitro anti-inflammatory effects of PP2A agonism were mediated by TTP activation.

conclusionsThe phosphorylation state of TTP is a critical determinant of inflammatory responses, and a tractable target for novel anti-inflammatory treatments.

Indexed as

Amino AlcoholsAnimalsApolipoproteins EArthritis, RheumatoidCytokinesDisease Models, AnimalEndothelial CellsEnzyme ActivationFibroblastsHumansMacrophagesMAP Kinase Signaling SystemMiceMice, Inbred C57BLMolecular Targeted Therapyp38 Mitogen-Activated Protein KinasesAAL(S) compoundAmino AlcoholsApolipoproteins ECOG1410Cytokinesp38 Mitogen-Activated Protein KinasesProtein Phosphatase 2RNA, MessengerSerineTristetraprolinZfp36 protein, mouseCytokinesFibroblastsInflammationRheumatoid ArthritisTNF-alpha

Identifiers

PMID27597652
PMCPMC5446007
OpenAlexW2517549119

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.