Evidence map›Paper›PMID 23525573›Full record

ArticleGut2014

Collagen degradation and neutrophilic infiltration: a vicious circle in inflammatory bowel disease.

Pim J Koelink, Saskia A Overbeek, Saskia Braber, Mary E Morgan, Paul A J Henricks, Mojtaba Abdul Roda, Hein W Verspaget, Simone C Wolfkamp, Anje A te Velde, Caleb W Jones and 7 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed, 1 pooled it
4.7field-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

94 citing papers in PubMed, 1 synthesis or guideline pooled it, 161 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Inflammatory bowel disease and extracellular matrix: when victim becomes double agent.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Review
  9. Review
  10. Proteases in intestinal health and disease.Nature reviews. Gastroenterology & hepatology · 2026
    Review
  11. Article
  12. Article
  13. Review
  14. Article
  15. The functional role of the extracellular matrix in inflammatory bowel disease associated gut fibrosis.Matrix biology : journal of the International Society for Matrix Biology · 2025
    Review
  16. Review
  17. Review
  18. Review
  19. Article
  20. Article

34 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

17 authors at 5 institutions in 2 countries.

Pim J KoelinkDivision of Pharmacology, Faculty of Science, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, , Utrecht, The Netherlands.
Saskia A Overbeek
Saskia Braber
Mary E Morgan
Paul A J Henricks
Mojtaba Abdul Roda
Hein W Verspaget
Simone C Wolfkamp
Anje A te Velde
Caleb W Jones
Patricia L Jackson
J Edwin Blalock
Rolf W Sparidans
John A W Kruijtzer
Johan Garssen
Gert Folkerts
Aletta D Kraneveld
Pharmo Institute · NLUtrecht University · NLUniversity of Alabama at Birmingham · USUniversity of Amsterdam · NLLeiden University Medical Center · NL

Funding

HL-A New Pathway for Neutrophil-induced Airway InflammationR01HL077783 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2006 to 2016
$3.2M
Acquired LTA4H Dysfunction in COPDR01HL110950 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2012 to 2015
$2.0M
Effect of Macrolide Treatment on a Novel Pathway of Neutrophilic Inflammation inR01HL090999 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2007 to 2010
$1.5M
PGP, A Possible Biomarker for COPD Exacerbations and or ProgressionR01HL114439 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2012 to 2015
$1.5M
Therapeutics for Chronic Lung Diseases: Antagonists of PGP, Chemokines and CXCRR01HL087824 · NHLBI · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI BLALOCK, J EDWIN · 2009 to 2010
$823k
MODELING OF CARDIAC ARRHYTHMIA GENERATORSF33HL007783 · NHLBI · UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR · PI GESELOWITZ, DAVID B. · 1988 to 1988
–
NHLBI NIH HHS HL07783NHLBI NIH HHS HL087824NHLBI NIH HHS HL90999NHLBI NIH HHS R01 HL077783NHLBI NIH HHS R01 HL087824NHLBI NIH HHS R01 HL090999NHLBI NIH HHS R01 HL110950NHLBI NIH HHS R01 HL114439
6 · The paper itself

Abstract

objectiveProline-glycine-proline (PGP) has been shown to have chemotactic effects on neutrophils via CXCR2 in several lung diseases. PGP is derived from collagen by the combined action of matrix metalloproteinase (MMP) 8 and/or MMP9 and prolyl endopeptidase (PE). We investigated the role of PGP in inflammatory bowel disease (IBD).

designIn intestinal tissue from patients with IBD and mice with dextran sodium sulfate (DSS)-induced colitis, MMP8, MMP9 and PE were evaluated by ELISA, immunoblot and immunohistochemistry. Peripheral blood polymorphonuclear cell (PMN) supernatants were also analysed accordingly and incubated with collagen to assess PGP generation ex vivo. PGP levels were measured by mass spectrometry, and PGP neutralisation was achieved with a PGP antagonist and PGP antibodies.

resultsIn the intestine of patients with IBD, MMP8 and MMP9 levels were elevated, while PE was expressed at similar levels to control tissue. PGP levels were increased in intestinal tissue of patients with IBD. Similar results were obtained in intestine from DSS-treated mice. PMN supernatants from patients with IBD were far more capable of generating PGP from collagen ex vivo than healthy controls. Furthermore, PGP neutralisation during DSS-induced colitis led to a significant reduction in neutrophil infiltration in the intestine.

conclusionsThe proteolytic cascade that generates PGP from collagen, as well as the tripeptide itself, is present in the intestine of patients with IBD and mice with DSS-induced colitis. PGP neutralisation in DSS-treated mice showed the importance of PGP-guided neutrophilic infiltration in the intestine and indicates a vicious circle in neutrophilic inflammation in IBD.

Indexed as

AdolescentAdultAgedAnimalsChildCollagenDisease Models, AnimalFemaleHumansInflammatory Bowel DiseasesIntestinal MucosaIntestinesMaleMatrix Metalloproteinase 8Matrix Metalloproteinase 9MiceCollagenMatrix Metalloproteinase 8Matrix Metalloproteinase 9PREPL protein, humanProlyl OligopeptidasesSerine Endopeptidases

Identifiers

PMID23525573
PMCPMC3963538
OpenAlexW2141988699

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.