ArticlePloS one2016
Investigating the Role of TNF-α and IFN-γ Activation on the Dynamics of iNOS Gene Expression in LPS Stimulated Macrophages.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 110 papers, 2 of them syntheses that pooled it.
What it found
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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.
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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.
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Who cites it
110 citing papers in PubMed, 2 syntheses or guidelines pooled it, 196 citations in OpenAlex.
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- Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review.Frontiers in immunology · 2024Pooled it
- Assessment of the Number and Phenotype of Macrophages in the Human BMB Samples of CML.BioMed research international · 2016Trial
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- Comparative Analysis of LPS/IFN-γ and LPS/ATP-Induced Inflammatory Models in BV2 Microglia.Neurochemical research · 2026Article
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- Dissecting bi-directional neuroimmune crosstalk in an in vitro model relevant to apical periodontitis.Scientific reports · 2026Article
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- IFN-γ-induced trained immunity enhances killing of priority pathogens in healthy and genetically vulnerable individuals.JCI insight · 2026Article
- Gene expression changes of homologs of human trained immunity markers in the silkworm (Bombyx mori) upon exposure to an innate immunity-enhancing agent.The Journal of veterinary medical science · 2026Article
- Ultrastructural Features, Immune Response, and Junctional Proteins in the Seminiferous Epithelium of SARS-CoV-2-Infected Mice.International journal of molecular sciences · 2026Article
- Nitric Oxide Signaling in Cardiovascular Physiology and Pathology: Mechanisms, Dysregulation, and Therapeutic Frontiers.International journal of molecular sciences · 2026Review
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- Deteriorating fractional exhaled nitric oxide preceding pneumonitis during immune checkpoint inhibitor therapy: a case report.Respiratory medicine case reports · 2026Article
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- Regional Variation in Antioxidant and Anti-Inflammatory Activities of the Brown AlgaBiomedicines · 2025Article
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- Sheep Pox Susceptibility: Role of Genetic Variants, Gene Expression, and Immune-Oxidative Markers.Veterinary sciences · 2025Article
- Reactive oxygen species and reactive nitrogen species are double-edged swords in Salmonella infection.Archives of microbiology · 2025Review
50 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophage produced inducible nitric oxide synthase (iNOS) is known to play a critical role in the proinflammatory response against intracellular pathogens by promoting the generation of bactericidal reactive nitrogen species. Robust and timely production of nitric oxide (NO) by iNOS and analogous production of reactive oxygen species are critical components of an effective immune response. In addition to pathogen associated lipopolysaccharides (LPS), iNOS gene expression is dependent on numerous proinflammatory cytokines in the cellular microenvironment of the macrophage, two of which include interferon gamma (IFN-γ) and tumor necrosis factor alpha (TNF-α). To understand the synergistic effect of IFN-γ and TNF-α activation, and LPS stimulation on iNOS expression dynamics and NO production, we developed a systems biology based mathematical model. Using our model, we investigated the impact of pre-infection cytokine exposure, or priming, on the system. We explored the essentiality of IFN-γ priming to the robustness of initial proinflammatory response with respect to the ability of macrophages to produce reactive species needed for pathogen clearance. Results from our theoretical studies indicated that IFN-γ and subsequent activation of IRF1 are essential in consequential production of iNOS upon LPS stimulation. We showed that IFN-γ priming at low concentrations greatly increases the effector response of macrophages against intracellular pathogens. Ultimately the model demonstrated that although TNF-α contributed towards a more rapid response time, measured as time to reach maximum iNOS production, IFN-γ stimulation was significantly more significant in terms of the maximum expression of iNOS and the concentration of NO produced.
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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.