Evidence map›Paper›PMID 27824650›Full record

ArticleInflammatory bowel diseases2016

VSL#3 Probiotic Stimulates T-cell Protein Tyrosine Phosphatase-mediated Recovery of IFN-γ-induced Intestinal Epithelial Barrier Defects.

Moorthy Krishnan, Harrison M Penrose, Nilay N Shah, Ronald R Marchelletta, Declan F McCole

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

Article in Inflammatory bowel diseases, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed, 1 pooled it
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

23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Antiviral Effects and Underlying Mechanisms of Probiotics as Promising Antivirals.Frontiers in cellular and infection microbiology · 2022
    Review
  10. Article
  11. Review
  12. Review
  13. Article
  14. Review
  15. Review
  16. Effects of dietary components on intestinal permeability in health and disease.American journal of physiology. Gastrointestinal and liver physiology · 2020
    Review
  17. Review
  18. Review
  19. Article
  20. Review
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

5 authors at 2 institutions in 1 country.

Moorthy Krishnan*Division of Biomedical Sciences, University of California, Riverside, California; and †Division of Gastroenterology, University of California, San Diego School of Medicine, La Jolla, California.
Harrison M Penrose
Nilay N Shah
Ronald R Marchelletta
Declan F McCole
University of California, San Diego · USUniversity of California, Riverside · US

Funding

Training Grant in GastroenterologyT32DK007202 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PRADIPTA · 1985 to 2022
$7.7M
A NOVEL ROLE FOR PTPN2 IN INTESTINAL EPITHELIAL BARRIER REGULATIONR01DK091281 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI Declan McCole · 2012 to 2026
$5.5M
NIDDK NIH HHS R01 DK091281NIDDK NIH HHS T32 DK007202
6 · The paper itself

Abstract

backgroundVSL#3 is a probiotic compound that has been used in the treatment of inflammatory bowel disease. T-cell protein tyrosine phosphatase (TCPTP) is the protein product of the inflammatory bowel disease candidate gene, PTPN2, and we have previously shown that it protects epithelial barrier function. The aim of this study was to investigate whether VSL#3 improves intestinal epithelial barrier function against the effects of the inflammatory bowel disease-associated proinflammatory cytokine, interferon-gamma (IFN-γ) through activation of TCPTP.

methodsPolarized monolayers of T84 intestinal epithelial cells were treated with increasing concentrations of VSL#3 to determine effects on TCPTP expression and enzymatic activity. Therapeutic effects of VSL#3 against barrier disruption by IFN-γ were measured by transepithelial electrical resistance and fluorescein isothiocyanate-dextran permeability. A novel TCPTP-deficient HT-29 intestinal epithelial cell line was generated to study the role of TCPTP in mediating the effects of VSL#3. Tight junction protein distribution was assessed with confocal microscopy.

resultsVSL#3 increased TCPTP protein levels and enzymatic activity, correlating with a VSL#3-induced decrease in IFN-γ signaling. VSL#3 corrected the decrease in transepithelial electrical resistance and the increase in epithelial permeability induced by IFN-γ. Moreover, the restorative effect of VSL#3 against IFN-γ signaling, epithelial permeability defects, altered expression and localization of the tight junction proteins claudin-2, occludin, and zonula occludens-1, were not realized in stable TCPTP/(PTPN2)-deficient HT-29 intestinal epithelial cells.

conclusionsVSL#3 reduces IFN-γ signaling and IFN-γ-induced epithelial barrier defects in a TCPTP-dependent manner. These data point to a key role for TCPTP as a therapeutic target for restoration of barrier function using probiotics.

Indexed as

Epithelial CellsHT29 CellsHumansInflammatory Bowel DiseasesInterferon-gammaIntestinal MucosaProbioticsProtein Tyrosine Phosphatase, Non-Receptor Type 2Tight JunctionsInterferon-gammaProtein Tyrosine Phosphatase, Non-Receptor Type 2PTPN2 protein, human

Identifiers

PMID27824650
PMCPMC5779620
OpenAlexW2546562258

What OpenQuestion holds

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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.