Evidence map›Paper›PMID 15479684›Full record

ArticleGut2004

Induction of T lymphocyte apoptosis by sulphasalazine in patients with Crohn's disease.

J Doering, B Begue, M J Lentze, F Rieux-Laucat, O Goulet, J Schmitz, N Cerf-Bensussan, F M Ruemmele

Open access · bronzeAbstract read
In one paragraph

Article in Gut, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.

0numbers the graph read from it
0cells of the map it votes in
37citing papers in PubMed
3.1field-weighted citation impact, top 9% 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

37 citing papers in PubMed, 98 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Article
  10. Is Having Inflammatory Bowel Disease a Risk Factor for Severe Acute Respiratory Syndrome Coronavirus 2?The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2022
    Article
  11. Apoptosis in peripheral blood lymphocytes in intestinal tuberculosis and Crohn's disease: Implications to diagnostic differentiation.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2020
    Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Review
  18. Article
  19. Role of DOR-β-arrestin1-Bcl2 signal transduction pathway and intervention effects of oxymatrine in ulcerative colitis.Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban · 2014
    Article
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 2 countries.

J DoeringHôpital Necker-Enfants Malades, Paediatric Gastroenterology, INSERM EMI 0212, University Paris V, 149, Rue de Sèvres, F-75743 Paris, Cedex 15, France.
B Begue
M J Lentze
F Rieux-Laucat
O Goulet
J Schmitz
N Cerf-Bensussan
F M Ruemmele
Inserm · FRUniversité Paris Cité · FRUniversity Hospital Bonn · DEUniversity of Bonn · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundLamina propria T lymphocytes (LPL) of the intestinal mucosa are chronically activated in Crohn's disease (CD). Defective apoptosis of activated LPL was proposed as a key pathogenic mechanism. In fact, increased expression of antiapoptotic molecules was observed in CD LPL. In the present work, we aimed to analyse the effects and underlying molecular mechanisms of 5-amino salicylic acid (5-ASA) and derivatives on apoptosis of LPL and peripheral blood lymphocytes (PBL) in patients with CD compared with ulcerative colitis (UC) and in non-inflammatory controls.

methodsPBL and LPL were isolated by Ficoll-Hypopaque gradient centrifugation and the EGTA-collagenase method, respectively. PBL/LPL were stimulated with FasL, 5-ASA, sulphapyridine, and sulphasalazine for 24/48 hours and apoptosis was quantified by flow cytometry (annexin V- propidium iodide method) and immunofluorescence. The molecular mechanisms of drug induced apoptosis were analysed in wild-type and FADD-/- Jurkat T cells using western blots and caspase assays.

resultsWhile PBL displayed a normal apoptosis pattern after Fas stimulation in patients with active CD, LPL from inflammatory areas were highly resistant. Comparable resistance to apoptosis was observed in LPL of UC patients. In contrast with 5-ASA, which did not induce apoptosis in lymphocytes, sulphasalazine proved to be a potent proapoptotic agent. Sulphasalazine induced T lymphocyte apoptosis was independent of the Fas pathway but associated with marked downregulation of antiapoptotic bcl-xl and bcl2, activation of the mitochondrial apoptosis signalling pathway, and subsequent activation of caspase-9 and caspase-3.

conclusionThe beneficial effect of sulphasalazine in treating inflammatory bowel disease is at least in part attributable to its proapoptotic effects on LPL which allows potent downregulation of lymphocyte activation.

Indexed as

AdolescentAdultAnti-Inflammatory Agents, Non-SteroidalApoptosisCells, CulturedChildChild, PreschoolColitis, UlcerativeCrohn DiseaseDose-Response Relationship, DrugHumansImmunity, MucosalIntestinal MucosaJurkat CellsLymphocyte ActivationMesalamineAnti-Inflammatory Agents, Non-SteroidalMesalamineSulfapyridineSulfasalazine

Identifiers

PMID15479684
PMCPMC1774288
OpenAlexW2111619432

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.