ArticleProceedings of the National Academy of Sciences of the United States of America2021
HIF-1α is a negative regulator of interferon regulatory factors: Implications for interferon production by hypoxic monocytes.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Dynamic metabolic programming of monocyte-derived cells defines immunity in CNS disease.Brain : a journal of neurology · 2026Review
- Porcine epidemic diarrhea virus promotes viral replication via ROS/HIF-1α-mediated glycolysis.Redox biology · 2026Article
- Review
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Hypoxia increases susceptibility of human intestinal epithelial cells to rotavirus infection through repression of interferon induction.Gut microbes · 2025Article
- Article
- Host-specific bacterial modulation of airway gene expression and alternative splicing.mSphere · 2025Article
- Mitochondrially Transcribed dsRNA Mediates Manganese-induced Neuroinflammation.bioRxiv : the preprint server for biology · 2025Article
- Metabolic Programming Drives Protective and Inflammatory Monocyte Fates in Viral Encephalitis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Transcription factor IRF-5 regulates lipid metabolism and mitochondrial function in murine CD8The EMBO journal · 2025Article
- Investigating the mechanism of Gentiopicroside in rheumatoid arthritis through network pharmacology, molecular docking, and experimental validation.Scientific reports · 2025Article
- Single-cell RNA sequencing of baseline PBMCs predicts ICI efficacy and irAE severity in patients with NSCLC.Journal for immunotherapy of cancer · 2025Article
- ALKBH4 functions as a hypoxia-responsive tumor suppressor and inhibits metastasis and tumorigenesis.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- Severe SARS-CoV-2 infection in diabetes was rescued in mice supplemented with metformin and/or αKG, and patients taking metformin, via HIF1α-IFN axis.Clinical and translational medicine · 2025Article
- Intracellular methylglyoxal accumulation in classically activated mouse macrophages is mediated by HIF-1α.Journal of leukocyte biology · 2025Article
- How oxygenation shapes immune responses: emerging roles for physioxia and pathological hypoxia.Nature reviews. Immunology · 2025Review
- A Mutant of Africa Swine Fever Virus Protein p72 Enhances Antibody Production and Regulates the Production of Cytokines.Viruses · 2025Article
- The role of type I interferon signaling in myeloid anti-tumor immunity.Frontiers in immunology · 2025Review
- HMGB1 derived from lung epithelial cells after cobalt nanoparticle exposure promotes the activation of lung fibroblasts.Nanotoxicology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Patients with severe COVID-19 infection exhibit a low level of oxygen in affected tissue and blood. To understand the pathophysiology of COVID-19 infection, it is therefore necessary to understand cell function during hypoxia. We investigated aspects of human monocyte activation under hypoxic conditions. HMGB1 is an alarmin released by stressed cells. Under normoxic conditions, HMGB1 activates interferon regulatory factor (IRF)5 and nuclear factor-κB in monocytes, leading to expression of type I interferon (IFN) and inflammatory cytokines including tumor necrosis factor α, and interleukin 1β, respectively. When hypoxic monocytes are activated by HMGB1, they produce proinflammatory cytokines but fail to produce type I IFN. Hypoxia-inducible factor-1α, induced by hypoxia, functions as a direct transcriptional repressor of IRF5 and IRF3. As hypoxia is a stressor that induces secretion of HMGB1 by epithelial cells, hypoxia establishes a microenvironment that favors monocyte production of inflammatory cytokines but not IFN. These findings have implications for the pathogenesis of COVID-19.
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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.