Evidence map›Paper›PMID 24873968›Full record

ArticlePloS one2014

Deficient production of reactive oxygen species leads to severe chronic DSS-induced colitis in Ncf1/p47phox-mutant mice.

Tiago Rodrigues-Sousa, Ana Filipa Ladeirinha, Ana Raquel Santiago, Helena Carvalheiro, Bruno Raposo, Ana Alarcão, António Cabrita, Rikard Holmdahl, Lina Carvalho, M Margarida Souto-Carneiro

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
2.0field-weighted citation impact, top 14% 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

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Preventive Effect ofMolecules (Basel, Switzerland) · 2023
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  5. Article
  6. Review
  7. From Flies to Men: ROS and the NADPH Oxidase in Phagocytes.Frontiers in cell and developmental biology · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. ROS in gastrointestinal inflammation: Rescue Or Sabotage?British journal of pharmacology · 2017
    Review
  14. Article
  15. Article
  16. Article
  17. Article
  18. Review
  19. 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

10 authors at 2 institutions in 2 countries.

Tiago Rodrigues-SousaImmunoMetabolic Pharmacology Group, CNC- Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
Ana Filipa LadeirinhaDepartamento de Anatomia Patológica, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
Ana Raquel SantiagoInstituto Biomédico de Investigação da Luz e Imagem, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
Helena CarvalheiroImmunoMetabolic Pharmacology Group, CNC- Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
Bruno RaposoMedical Inflammation Research, Karolinska Institute, Stockholm, Sweden.
Ana AlarcãoDepartamento de Anatomia Patológica, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
António CabritaDepartamento de Patologia Experimental, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
Rikard HolmdahlMedical Inflammation Research, Karolinska Institute, Stockholm, Sweden.
Lina CarvalhoDepartamento de Anatomia Patológica, Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.
M Margarida Souto-CarneiroImmunoMetabolic Pharmacology Group, CNC- Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
University of Coimbra · PTKarolinska Institutet · SE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundColitis is a common clinical complication in chronic granulomatous disease (CGD), a primary immunodeficiency caused by impaired oxidative burst. Existing experimental data from NADPH-oxidase knockout mice propose contradictory roles for the involvement of reactive oxygen species in colitis chronicity and severity. Since genetically controlled mice with a point-mutation in the Ncf1 gene are susceptible to chronic inflammation and autoimmunity, we tested whether they presented increased predisposition to develop chronic colitis.

methodsColitis was induced in Ncf1-mutant and wild-type mice by a 1st 7-days cycle of dextran sulfate sodium (DSS), intercalated by a 7-days resting period followed by a 2nd 7-days DSS-cycle. Cytokines were quantified locally in the colon inflammatory infiltrates and in the serum. Leukocyte infiltration and morphological alterations of the colon mucosa were assessed by immunohistochemistry.

resultsClinical scores demonstrated a more severe colitis in Ncf1-mutant mice than controls, with no recovery during the resting period and a severe chronic colitis after the 2nd cycle, confirmed by histopathology and presence of infiltrating neutrophils, macrophages, plasmocytes and lymphocytes in the colon. Severe colitis was mediated by increased local expression of cytokines (IL-6, IL-10, TNF-α, IFN-γ and IL-17A) and phosphorylation of Leucine-rich repeat kinase 2 (LRRK2). Serological cytokine titers of those inflammatory cytokines were more elevated in Ncf1-mutant than control mice, and were accompanied by systemic changes in functional subsets of monocytes, CD4+ T and B cells.

conclusionThis suggests that an ineffective oxidative burst leads to severe chronic colitis through local accumulation of peroxynitrites, pro-inflammatory cytokines and lymphocytes and systemic immune deregulation similar to CGD.

Indexed as

MutationAnimalsChronic DiseaseColitisCytokinesDextran SulfateDisease Models, AnimalInflammation MediatorsIntestinal MucosaLeucine-Rich Repeat Serine-Threonine Protein Kinase-2LeukocytesMaleMiceMice, KnockoutNADPH OxidasesPhenotypeCytokinesDextran SulfateInflammation MediatorsLeucine-Rich Repeat Serine-Threonine Protein Kinase-2Lrrk2 protein, mouseNADPH Oxidasesneutrophil cytosolic factor 1Protein Serine-Threonine KinasesReactive Oxygen Species

Identifiers

PMID24873968
PMCPMC4038546
OpenAlexW2088863626

What OpenQuestion holds

Textmetadata
LicenceCC BY
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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.