ArticleThe Journal of experimental medicine2013
Nitric oxide-mediated regulation of ferroportin-1 controls macrophage iron homeostasis and immune function in Salmonella infection.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 114 papers.
What it found
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Who cites it
114 citing papers in PubMed, 207 citations in OpenAlex.
- Host-microbiota-pathogen interactions drive Salmonella enterica serovar Typhimurium pathogenesis.Nature reviews. Microbiology · 2026Review
- Regulatory interplay between nitric oxide and heme in redox signaling and inflammation.Redox biology · 2026Review
- Iron as an immunometabolic signal in infection and inflammation.Frontiers in immunology · 2026Review
- Loss of NR2F6 Protects from Salmonella Typhimurium Infection.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- RNA Sequence Analysis in Macrophages Infected With Trypanosoma cruzi: Focus on TLR2 and TLR7, Iron Metabolism, and Extracellular Matrix Biosynthesis.The Journal of infectious diseases · 2025Article
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- Article
- Iron, Hepcidin, and Immunity.Advances in experimental medicine and biology · 2025Review
- Macrophage metabolism in inflammatory heart disease: new insights and therapeutic implications.Frontiers in medicine · 2025Review
- Research progress of macrophage ferroptosis in inflammatory bowel disease and inflammation-cancer transformation.Frontiers in immunology · 2025Review
- Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections.Infection and immunity · 2024Review
- Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles.Frontiers in immunology · 2024Review
- Revisiting the role of hypoxia-inducible factors and nuclear factor erythroid 2-related factor 2 in regulating macrophage inflammation and metabolism.Frontiers in cellular and infection microbiology · 2024Review
- Biology of Anemia: A Public Health Perspective.The Journal of nutrition · 2023Article
- Nrf2 regulates iron-dependent hippocampal synapses and functional connectivity damage in depression.Journal of neuroinflammation · 2023Article
- Heat-Labile Enterotoxin Decreases Macrophage Phagocytosis of EnterotoxigenicMicroorganisms · 2023Article
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- Advances in Ferritin Physiology and Possible Implications in Bacterial Infection.International journal of molecular sciences · 2023Review
- Continuous Measurement of Reactive Oxygen Species Formation in Bacteria-infected Bone Marrow-derived Macrophages Using a Fluorescence Plate Reader.Bio-protocol · 2023Article
- Iron as a therapeutic target in chronic liver disease.World journal of gastroenterology · 2023Review
54 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 8 institutions in 3 countries.
Funding
Abstract
Nitric oxide (NO) generated by inducible NO synthase 2 (NOS2) affects cellular iron homeostasis, but the underlying molecular mechanisms and implications for NOS2-dependent pathogen control are incompletely understood. In this study, we found that NO up-regulated the expression of ferroportin-1 (Fpn1), the major cellular iron exporter, in mouse and human cells. Nos2(-/-) macrophages displayed increased iron content due to reduced Fpn1 expression and allowed for an enhanced iron acquisition by the intracellular bacterium Salmonella typhimurium. Nos2 gene disruption or inhibition of NOS2 activity led to an accumulation of iron in the spleen and splenic macrophages. Lack of NO formation resulted in impaired nuclear factor erythroid 2-related factor-2 (Nrf2) expression, resulting in reduced Fpn1 transcription and diminished cellular iron egress. After infection of Nos2(-/-) macrophages or mice with S. typhimurium, the increased iron accumulation was paralleled by a reduced cytokine (TNF, IL-12, and IFN-γ) expression and impaired pathogen control, all of which were restored upon administration of the iron chelator deferasirox or hyperexpression of Fpn1 or Nrf2. Thus, the accumulation of iron in Nos2(-/-) macrophages counteracts a proinflammatory host immune response, and the protective effect of NO appears to partially result from its ability to prevent iron overload in macrophages.
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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.