Evidence map›Paper›PMID 25706292›Full record

ArticlePloS one2015

Natural indoles, indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM), attenuate staphylococcal enterotoxin B-mediated liver injury by downregulating miR-31 expression and promoting caspase-2-mediated apoptosis.

Philip B Busbee, Mitzi Nagarkatti, Prakash S Nagarkatti

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed
1.8field-weighted citation impact, top 17% 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

34 citing papers in PubMed, 50 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Targeting AhR as a Novel Therapeutic Modality against Inflammatory Diseases.International journal of molecular sciences · 2021
    Review
  9. Article
  10. Article
  11. Review
  12. Immune and microRNA responses toWorld journal of gastroenterology · 2020
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  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

3 authors at 1 institution in 1 country.

Philip B BusbeeDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
Mitzi NagarkattiDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America; WJB Dorn Veterans Affairs Medical Center, Columbia, South Carolina, United States of America.
Prakash S NagarkattiDepartment of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, South Carolina, United States of America.
University of South Carolina · US

Funding

Targeting early ceramide elevation in pre-symptomatic eczemaP20GM103641 · NIGMS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI ENOS, REILLY, NAGARKATTI, PRAKASH S · 2012 to 2023
$20.7M
Use of Resveratrol to treat experimental multiple sclerosisP01AT003961 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2007 to 2018
$14.2M
Role of natural indoles in experimental autoimmune encephalomyelitisR01AT006888 · NCCIH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI · 2011 to 2015
$2.0M
Immunopathological basis of PTSDR01MH094755 · NIMH · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, PRAKASH S · 2011 to 2015
$1.7M
Estrogen-T cell InteractionsR01ES019313 · NIEHS · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI NAGARKATTI, MITZI, NAGARKATTI, PRAKASH S · 2010 to 2014
$1.5M
BLRD VA I01 BX001357NCCIH NIH HHS P01 AT003961NCCIH NIH HHS P01-AT003961NCCIH NIH HHS R01 AT006888NCCIH NIH HHS R01-AT006888NIEHS NIH HHS R01 ES019313NIEHS NIH HHS R01-ES019313NIGMS NIH HHS P20 GM103641NIGMS NIH HHS P20-GM103641NIMH NIH HHS R01 MH094755NIMH NIH HHS R01-MH094755
6 · The paper itself

Abstract

Staphylococcal enterotoxin B (SEB) is a potent superantigen capable of inducing inflammation characterized by robust immune cell activation and proinflammatory cytokine release. Exposure to SEB can result in food poisoning as well as fatal conditions such as toxic shock syndrome. In the current study, we investigated the effect of natural indoles including indole-3-carbinol (I3C) and 3,3'-diindolylmethane (DIM) on SEB-mediated liver injury. Injection of SEB into D-galactosamine-sensitized female C57BL/6 mice resulted in liver injury as indicated by an increase in enzyme aspartate transaminase (AST) levels, induction of inflammatory cytokines, and massive infiltration of immune cells into the liver. Administration of I3C and DIM (40 mg/kg), by intraperitonal injection, attenuated SEB-induced acute liver injury, as evidenced by decrease in AST levels, inflammatory cytokines and cellular infiltration in the liver. I3C and DIM triggered apoptosis in SEB-activated T cells primarily through activation of the intrinsic mitochondrial pathway. In addition, inhibitor studies involving caspases revealed that I3C and DIM-mediated apoptosis in these activated cells was dependent on caspase-2 but independent of caspase-8, 9 and 3. In addition, I3C and DIM caused a decrease in Bcl-2 expression. Both compounds also down-regulated miR-31, which directly targets caspase-2 and influences apoptosis in SEB-activated cells. Our data demonstrate for the first time that indoles can effectively suppress acute hepatic inflammation caused by SEB and that this may be mediated by decreased expression of miR-31 and consequent caspase-2-dependent apoptosis in T cells.

Indexed as

AnimalsApoptosisAspartate AminotransferasesBlotting, WesternCaspase 2Chemical and Drug Induced Liver InjuryCytokinesDown-RegulationEnterotoxinsFemaleIndolesInflammation MediatorsLiverMice, Inbred C57BLMicroRNAsProto-Oncogene Proteins c-bcl-23,3'-diindolylmethaneAspartate AminotransferasesCaspase 2Cytokinesenterotoxin B, staphylococcalEnterotoxinsindole-3-carbinolIndolesInflammation MediatorsMicroRNAsMirn31 microRNA, mouseProto-Oncogene Proteins c-bcl-2

Identifiers

PMID25706292
PMCPMC4338211
OpenAlexW2074384261

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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.