Evidence map›Paper›PMID 21343355›Full record

ArticleInfection and immunity2011

Epithelial phosphatidylinositol-3-kinase signaling is required for β-catenin activation and host defense against Citrobacter rodentium infection.

Jeffrey B Brown, Paul Cheresh, Tatiana Goretsky, Elizabeth Managlia, Gery R Grimm, Hyunji Ryu, Mojgan Zadeh, Ramanarao Dirisina, Terrence A Barrett

Open access · greenAbstract read
In one paragraph

Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

29 citing papers in PubMed, 44 citations in OpenAlex.

  1. Myo-inositol reduces β-catenin activation in colitis.World journal of gastroenterology · 2017
    Trial
  2. Article
  3. Article
  4. Article
  5. Review
  6. A Protective Role of Canonical Wnt/Mediators of inflammation · 2024
    Review
  7. Transcriptional Studies onFrontiers in cellular and infection microbiology · 2021
    Review
  8. Article
  9. Article
  10. Article
  11. Frontiers in immunology · 2018
    Article
  12. Aquaporin-3 mediates hydrogen peroxide-dependent responses to environmental stress in colonic epithelia.Proceedings of the National Academy of Sciences of the United States of America · 2017
    Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  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

9 authors at 2 institutions in 1 country.

Jeffrey B BrownDepartment of Pediatrics, Northwestern University Feinberg School of Medicine/Children's Memorial Hospital, Chicago, IL 60611, USA.
Paul Cheresh
Tatiana Goretsky
Elizabeth Managlia
Gery R Grimm
Hyunji Ryu
Mojgan Zadeh
Ramanarao Dirisina
Terrence A Barrett
Northwestern University · USLurie Children's Hospital · US

Funding

T CELL ACTIVATION AND CRYPT CELL APOPTOSISR01DK054778 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BARRETT, TERRENCE A. · 1999 to 2008
$3.0M
Lymphoepithelial interactions in IBDR01AI061701 · NIAID · NORTHWESTERN UNIVERSITY AT CHICAGO · PI BARRETT, TERRENCE A. · 2005 to 2009
$1.5M
P-selectin in effector T cell recruitment to the colonK08DK066161 · NIDDK · LURIE CHILDREN'S HOSPITAL OF CHICAGO · PI BROWN, JEFFREY B. · 2005 to 2009
$646k
NIAID NIH HHS R01 AI061701NIDDK NIH HHS DK066161NIDDK NIH HHS DK54778NIDDK NIH HHS K08 DK066161NIDDK NIH HHS R01 DK054778PHS HHS DKAI061701
6 · The paper itself

Abstract

Citrobacter rodentium infection of mice induces cell-mediated immune responses associated with crypt hyperplasia and epithelial β-catenin signaling. Recent data suggest that phosphatidylinositol-3-kinase (PI3K)/Akt signaling cooperates with Wnt to activate β-catenin in intestinal stem and progenitor cells through phosphorylation at Ser552 (P-β-catenin(552)). Our aim was to determine whether epithelial PI3K/Akt activation is required for β-catenin signaling and host defense against C. rodentium. C57BL/6 mice were infected with C. rodentium and treated with dimethyl sulfoxide (DMSO) (vehicle control) or with the PI3K inhibitor LY294002 or wortmannin. The effects of infection on PI3K activation and β-catenin signaling were analyzed by immunohistochemistry. The effects of PI3K inhibition on host defense were analyzed by the quantification of splenic and colon bacterial clearance, and adaptive immune responses were measured by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). Increased numbers of P-β-catenin(552)-stained epithelial cells were found throughout expanded crypts in C. rodentium colitis. We show that the inhibition of PI3K signaling attenuates epithelial Akt activation, the Ser552 phosphorylation and activation of β-catenin, and epithelial cell proliferative responses during C. rodentium infection. PI3K inhibition impairs bacterial clearance despite having no impact on mucosal cytokine (gamma interferon [IFN-γ], tumor necrosis factor [TNF], interleukin-17 [IL-17], and IL-1β) or chemokine (CXCL1, CXCL5, CXCL9, and CXCL10) induction. The results suggest that the host defense against C. rodentium requires epithelial PI3K activation to induce Akt-mediated β-catenin signaling and the clearance of C. rodentium independent of adaptive immune responses.

Indexed as

Animalsbeta CateninCitrobacter rodentiumColitisEnterobacteriaceae InfectionsEnzyme ActivationEnzyme InhibitorsEnzyme-Linked Immunosorbent AssayEpithelial CellsFluorescent Antibody TechniqueImmunohistochemistryMiceMice, Inbred C57BLPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-aktReverse Transcriptase Polymerase Chain Reactionbeta CateninEnzyme InhibitorsPhosphatidylinositol 3-KinasesProto-Oncogene Proteins c-akt

Identifiers

PMID21343355
PMCPMC3088123
OpenAlexW2100403561

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.