Evidence map›Paper›PMID 28096401›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2017

Ornithine decarboxylase regulates M1 macrophage activation and mucosal inflammation via histone modifications.

Dana M Hardbower, Mohammad Asim, Paula B Luis, Kshipra Singh, Daniel P Barry, Chunying Yang, Meredith A Steeves, John L Cleveland, Claus Schneider, M Blanca Piazuelo and 2 more

Registry-linked trialOpen access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05042024 (Supplementation With L-ornithine Increases Representation Density of CD68+ and CD163+ Macrophages in Human Periodontitis Gingiva and Can Modulate Macrophages Phenotypes. Randomized Controlled Pilot Trial), which is not on this map. Cited by 149 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
149citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 2% 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.

NCT05042024 phase3completednot on this map

Supplementation With L-ornithine Increases Representation Density of CD68+ and CD163+ Macrophages in Human Periodontitis Gingiva and Can Modulate Macrophages Phenotypes. Randomized Controlled Pilot Trial

TypeinterventionalSponsorUkrainian Medical Stomatological AcademyRan2017 to 2018Enrolled75ConditionsPeriodontitisArmsScaling and root planing, Oral L-arginine aspartate administration, Oral L-ornithine aspartate administration
3 · Its place in the literature

Who cites it

149 citing papers in PubMed, 1 synthesis or guideline pooled it, 218 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Review
  6. IL-9R/Arg1 pathway promotes polyamine metabolism in human airway macrophages.The Journal of allergy and clinical immunology · 2026
    Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Review
  13. ODC1 restricts meningeal B cell age-associated-like phenotype and function in multiple sclerosis: A human and experimental study.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Review
  19. Article
  20. Article

89 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 1 country.

Dana M HardbowerDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
Mohammad AsimDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
Paula B LuisDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
Kshipra SinghDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
Daniel P BarryDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
Chunying YangDepartment of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612.
Meredith A SteevesDepartment of Cancer Biology, The Scripps Research Institute, Jupiter, FL 33458.
John L ClevelandDepartment of Tumor Biology, Moffitt Cancer Center and Research Institute, Tampa, FL 33612.
Claus SchneiderDepartment of Pharmacology, Vanderbilt University School of Medicine, Nashville, TN 37232.
M Blanca PiazueloDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
Alain P GobertDivision of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
Keith T WilsonDepartment of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232; keith.wilson@vanderbilt.edu.
Vanderbilt University Medical Center · USScripps Research Institute · USVanderbilt University · USVA Tennessee Valley Healthcare System · US

Funding

Tumor Immunology and Microenvironment Research ProgramP30CA068485 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI STACIE B DUSETZINA · 1995 to 2026
$172.8M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Role of Iron and B-Catenin Activation in Gastric CarcinogenesisP01CA116087 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Kevin L Schey · 2009 to 2026
$27.5M
Project 3 - Molecular Signatures of Gastric Carcinogenesis in the Host Response to H. pyloriP01CA028842 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1985 to 2019
$15.8M
TRAINING PROGRAM IN CELLULAR, BIOCHEMICAL, &MOLECULAR ST32GM008554 · NIGMS · VANDERBILT UNIVERSITY · PI PATTON, JAMES G. · 1995 to 2020
$7.4M
Immunomodulatory effects of arginine supplementation in colitis and colon cancerR01AT004821 · NCCIH · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 2008 to 2017
$4.0M
HPYLORI INDUCED DNA DAMAGE AND IMMUNE DYSREGULATIONR01DK053620 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WILSON, KEITH T. · 1997 to 2014
$3.4M
Targeted chemoprevention of gastric carcinogenesis in high risk populationsR01CA190612 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI MORGAN, DOUGLAS, WILSON, KEITH T. · 2014 to 2018
$3.0M
Oxidative activation of the dietary cancer chemopreventive agent curcuminR01AT006896 · NCCIH · VANDERBILT UNIVERSITY · PI SCHNEIDER, CLAUS · 2013 to 2017
$2.2M
EGFR Signaling in Macrophages: A Novel Regulator of Immune Responses to H. pyloriF31DK107159 · NIDDK · VANDERBILT UNIVERSITY · PI HARDBOWER, DANA M. · 2015 to 2016
$56k
Arginine Availability and Metabolism in the Immune Evasion of H. pyloriI01BX001453 · VA · VETERANS HEALTH ADMINISTRATION · PI WILSON, KEITH T. · 2012 to 2019
–
BLRD VA I01 BX001453NCCIH NIH HHS R01 AT004821NCCIH NIH HHS R01 AT006896NCI NIH HHS P01 CA028842NCI NIH HHS P01 CA116087NCI NIH HHS P30 CA068485NCI NIH HHS R01 CA190612NIDDK NIH HHS F31 DK107159NIDDK NIH HHS P30 DK058404NIDDK NIH HHS R01 DK053620NIGMS NIH HHS T32 GM008554
6 · The paper itself

Abstract

Macrophage activation is a critical step in host responses during bacterial infections. Ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine metabolism, has been well studied in epithelial cells and is known to have essential roles in many different cellular functions. However, its role in regulating macrophage function during bacterial infections is not well characterized. We demonstrate that macrophage-derived ODC is a critical regulator of M1 macrophage activation during both Helicobacter pylori and Citrobacter rodentium infection. Myeloid-specific Odc deletion significantly increased gastric and colonic inflammation, respectively, and enhanced M1 activation. Add-back of putrescine, the product of ODC, reversed the increased macrophage activation, indicating that ODC and putrescine are regulators of macrophage function. Odc-deficient macrophages had increased histone 3, lysine 4 (H3K4) monomethylation, and H3K9 acetylation, accompanied by decreased H3K9 di/trimethylation both in vivo and ex vivo in primary macrophages. These alterations in chromatin structure directly resulted in up-regulated gene transcription, especially M1 gene expression. Thus, ODC in macrophages tempers antimicrobial, M1 macrophage responses during bacterial infections through histone modifications and altered euchromatin formation, leading to the persistence and pathogenesis of these organisms.

Indexed as

AnimalsCell LineCitrobacter rodentiumColitisColonCytokinesEnterobacteriaceae InfectionsGastric MucosaGastritisHelicobacter InfectionsHelicobacter pyloriHistonesHumansMacrophage ActivationMacrophagesMaleCytokinesHistonesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mouseOrnithine DecarboxylasePutrescineHelicobacter pylorihistone modificationsmacrophage polarizationornithine decarboxylasepolyamines

Identifiers

PMID28096401
PMCPMC5293075
OpenAlexW2576339630

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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.