ArticleGastroenterology2010
Polyamines Impair Immunity to Helicobacter pylori by Inhibiting L-Arginine Uptake Required for Nitric Oxide Production.
Article in Gastroenterology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 102 citations in OpenAlex.
- Safety and Efficacy of Eflornithine in Patients with Gastric Precancerous Lesions: A Double-Blinded, Randomized Clinical Trial.Cancer prevention research (Philadelphia, Pa.) · 2026Trial
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Androgen Receptor Drives Polyamine Synthesis, Creating a Vulnerability for Prostate Cancer.Cancer research · 2026Article
- The Multi-dimensional Mechanisms and Transformation Prospects of the Intratumoral Microbiota-Arginine Metabolism Axis in Tumor Progression and Immune Regulation.International journal of medical sciences · 2026Review
- Single-cell transcriptomic profiling uncovers cellular complexity and microenvironment in gastric tumorigenesis associated with Helicobacter pylori.Journal of advanced research · 2025Article
- Genome-wide association study of post COVID-19 syndrome in a population-based cohort in Germany.Scientific reports · 2025Article
- Polyamine metabolism in prostate cancer.Current opinion in oncology · 2025Review
- Spermine oxidase promotes Helicobacter pylori-mediated gastric carcinogenesis through acrolein production.Oncogene · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Alterations in polyamine metabolism induced by the pathogen Helicobacter pylori: Implications for gastric inflammation and carcinogenesis.Methods in enzymology · 2025Article
- Anti-inflammatory effects of 1,7-dihydroxy-3,4-dimethoxyxanthone through inhibition of M1-phenotype macrophages via arginine/mitochondrial axis.Immunologic research · 2024Article
- Article
- Salmonella Typhimurium exploits host polyamines for assembly of the type 3 secretion machinery.PLoS biology · 2024Article
- Analysis of the effect of hypusination in myeloid cells on colitis and colitis-associated cancer.Heliyon · 2024Article
- Modulation of Gut Microbial Biomarkers and Metabolites in Cancer Management by Tea Compounds.International journal of molecular sciences · 2024Review
- Involvement of mammalian SoLute Carriers (SLC) in the traffic of polyamines.Frontiers in molecular biosciences · 2024Review
- Involvement of Nitric Oxide in Protecting against Radical Species and Autoregulation of M1-Polarized Macrophages through Metabolic Remodeling.Molecules (Basel, Switzerland) · 2023Review
- Mitochondrial Function in Health and Disease: Responses to Helicobacter pylori Metabolism and Impact in Gastric Cancer Development.Current topics in microbiology and immunology · 2023Article
- Ornithine Decarboxylase in Gastric Epithelial Cells Promotes the Immunopathogenesis ofJournal of immunology (Baltimore, Md. : 1950) · 2022Article
- Interrogation of T Cell-Enriched Tumors Reveals Prognostic and Immunotherapeutic Implications of Polyamine Metabolism.Cancer research communications · 2022Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsHelicobacter pylori-induced immune responses fail to eradicate the bacterium. Nitric oxide (NO) can kill H pylori. However, translation of inducible NO synthase (iNOS) and NO generation by H pylori-stimulated macrophages is inhibited by the polyamine spermine derived from ornithine decarboxylase (ODC), and is dependent on availability of the iNOS substrate L-arginine (L-Arg). We determined if spermine inhibits iNOS-mediated immunity by reducing L-Arg uptake into macrophages.
methodsLevels of the inducible cationic amino acid transporter (CAT)2, ODC, and iNOS were measured in macrophages and H pylori gastritis tissues. L-Arg uptake, iNOS expression, and NO levels were assessed in cells with small interfering RNA knockdown of CAT2 or ODC, and in gastric macrophages. The ODC inhibitor, α-difluoromethylornithine, was administered to H pylori-infected mice for 4 months after inoculation.
resultsH pylori induced CAT2 and uptake of L-Arg in RAW 264.7 or primary macrophages. Addition of spermine or knockdown of CAT2 inhibited L-Arg uptake, NO production, and iNOS protein levels, whereas knockdown of ODC had the opposite effect. CAT2 and ODC were increased in mouse and human H pylori gastritis tissues and localized to macrophages. Gastric macrophages from H pylori-infected mice showed increased ODC expression, and attenuated iNOS and NO levels upon ex vivo H pylori stimulation versus cells from uninfected mice. α-Difluoromethylornithine treatment of infected mice restored L-Arg uptake, iNOS protein expression, and NO production in gastric macrophages, and significantly reduced both H pylori colonization levels and gastritis severity.
conclusionsUp-regulation of ODC in gastric macrophages impairs host defense against H pylori by suppressing iNOS-derived NO production.
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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.