Trial reportJournal of immunology (Baltimore, Md. : 1950)2014
Epigenetic silencing of the human NOS2 gene: rethinking the role of nitric oxide in human macrophage inflammatory responses.
Trial report in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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.
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.
Who cites it
81 citing papers in PubMed, 131 citations in OpenAlex.
- Regulation of Inducible Nitric Oxide Synthase (NOS2) Expression in Healthy and Inflamed Bowel: A Narrative Review.International journal of molecular sciences · 2026Review
- Nitric oxide-driven Warburg reprogramming at the NOS2-COX2 axis: An integrative engine of cancer hallmarks.Redox biology · 2026Review
- Piezo1 accelerates osteoarthritis progression via promotion of HBB-dependent oxidative phosphorylation.The Journal of biological chemistry · 2026Article
- iNOS modulates inflammatory responses in an NO-independent manner through direct interaction with IRG1 in mitochondria.Nature metabolism · 2026Article
- Species-specific iNOS expression distinguishes epithelial and myeloid IFNγ responses in tuberculosis.bioRxiv : the preprint server for biology · 2026Article
- Dissecting antimicrobial logic: species-specific strategies for intracellular pathogen defense.mSphere · 2025Review
- Macrophages say NO to nucleotide synthesis and salvage instead.Nature metabolism · 2025Article
- Deep metabolic profiling of immune cells by spectral flow cytometry-A comprehensive validation approach.iScience · 2025Article
- Differences between human and rodent nitric oxide production dictate susceptibility to tick-bornebioRxiv : the preprint server for biology · 2025Article
- Arginine metabolism in myeloid cells in health and disease.Seminars in immunopathology · 2025Review
- Extracellular vesicles shed by macrophages co-cultured withBioscience of microbiota, food and health · 2025Article
- Model systems to studyFrontiers in cellular and infection microbiology · 2025Review
- Network biomarkers of Alzheimer's disease risk derived from joint volume and texture covariance patterns in mouse models.PloS one · 2025Article
- Brain network fingerprints of Alzheimer's disease risk factors in mouse models with humanized APOE alleles.Magnetic resonance imaging · 2024Article
- Potential Beneficial Role of Nitric Oxide in SARS-CoV-2 Infection: Beyond Spike-Binding Inhibition.Antioxidants (Basel, Switzerland) · 2024Article
- Type I interferon governs immunometabolic checkpoints that coordinate inflammation during Staphylococcal infection.Cell reports · 2024Article
- APOE, Immune Factors, Sex, and Diet Interact to Shape Brain Networks in Mouse Models of Aging.bioRxiv : the preprint server for biology · 2024Article
- Human airway epithelium controlsFrontiers in immunology · 2024Article
- Cytokine-Induced iNOS in A549 Alveolar Epithelial Cells: A Potential Role in COVID-19 Lung Pathology.Biomedicines · 2023Article
- Targeting Nitric Oxide: Say NO to Metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Review
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Macrophages, including alveolar macrophages, are primary phagocytic cells of the innate immune system. Many studies of macrophages and inflammation have been done in mouse models, in which inducible NO synthase (NOS2) and NO are important components of the inflammatory response. Human macrophages, in contrast to mouse macrophages, express little detectable NOS2 and generate little NO in response to potent inflammatory stimuli. The human NOS2 gene is highly methylated around the NOS2 transcription start site. In contrast, mouse macrophages contain unmethylated cytosine-phosphate-guanine (CpG) dinucleotides proximal to the NOS2 transcription start site. Further analysis of chromatin accessibility and histone modifications demonstrated a closed conformation at the human NOS2 locus and an open conformation at the murine NOS2 locus. In examining the potential for CpG demethylation at the NOS2 locus, we found that the human NOS2 gene was resistant to the effects of demethylation agents both in vitro and in vivo. Our data demonstrate that epigenetic modifications in human macrophages are associated with CpG methylation, chromatin compaction, and histone modifications that effectively silence the NOS2 gene. Taken together, our findings suggest there are significant and underappreciated differences in how murine and human macrophages respond to inflammatory stimuli.
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What OpenQuestion holds
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.