ArticleImmunology2010
Hypoxic stress up-regulates the expression of Toll-like receptor 4 in macrophages via hypoxia-inducible factor.
Article in Immunology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed, 174 citations in OpenAlex.
- Gestational diabetes mellitus in women increased the risk of neonatal infection via inflammation and autophagy in the placenta.Medicine · 2020Trial
- Neuroprotective effects of piracetam in vascular dementia: a review of toll-like receptor 4 -mediated neuroinflammatory pathways.Inflammopharmacology · 2026Review
- The Mechanism of NLRP3 Inflammasome Activation and Its Roles in Chronic Rhinosinusitis.World journal of otorhinolaryngology - head and neck surgery · 2026Review
- Mechanism of HIF-1α-mediated angiogenesis in rheumatoid arthritis and progress of natural medicine interventions.Frontiers in pharmacology · 2026Review
- From mechanisms to therapeutics: molecular insights into gastrointestinal injury under high-altitude hypoxia.Frontiers in microbiology · 2026Review
- Tetrandrine enhances cognition in SAH rats via gut microbiota CYP51 and TLR4 signaling.Scientific reports · 2025Article
- Disseminated intravascular coagulation.Journal of intensive care · 2025Review
- Article
- A Hypoxia-Inflammation Cycle and Multiple Sclerosis: Mechanisms and Therapeutic Implications.Current treatment options in neurology · 2025Review
- Endothelial HSPA12B regulates myocardial monocyte infiltration and inflammatory activity after myocardial infarction.Frontiers in immunology · 2025Article
- Hypobaric hypoxia aggravates neuroinflammation in ligature-induced periodontitis mice via the STAT3 signaling pathway.Frontiers in immunology · 2025Article
- The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation.Cell reports · 2024Article
- Protective Role of MAVS Signaling for Murine Lipopolysaccharide-Induced Acute Kidney Injury.ImmunoHorizons · 2024Article
- Hypoxic Effects on Matrix Metalloproteinases' Expression in the Tumor Microenvironment and Therapeutic Perspectives.International journal of molecular sciences · 2023Review
- Hypoxia-Inducible Factor 1α and Its Role in Lung Injury: Adaptive or Maladaptive.Inflammation · 2023Review
- Mechanisms of Maternal Diet-Induced Obesity Affecting the Offspring Brain and Development of Affective Disorders.Metabolites · 2023Review
- Neonatal asphyxia as an inflammatory disease: Reactive oxygen species and cytokines.Frontiers in pediatrics · 2023Review
- The Role of Inflammation in Cognitive Impairment of Obstructive Sleep Apnea Syndrome.Brain sciences · 2022Review
- Immunometabolic rewiring of tubular epithelial cells in kidney disease.Nature reviews. Nephrology · 2022Review
- Inflammatory gene expression during acute high-altitude exposure.The Journal of physiology · 2022Article
30 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) are germline-encoded innate immune receptors that recognize invading micro-organisms and induce immune and inflammatory responses. Deregulation of TLRs is known to be closely linked to various immune disorders and inflammatory diseases. Cells at sites of inflammation are exposed to hypoxic stress, which further aggravates inflammatory processes. We have examined if hypoxic stress modulates the TLR activity of macrophages. Hypoxia and CoCl(2) (a hypoxia mimetic) enhanced the expression of TLR4 messenger RNA and protein in macrophages (RAW264.7 cells), whereas the messenger RNA of other TLRs was not increased. To determine the underlying mechanism, we investigated the role of hypoxia-inducible factor 1 (HIF-1) in the regulation of TLR4 expression. Knockdown of HIF-1alpha expression by small interfering RNA inhibited hypoxia-induced and CoCl(2)-induced TLR4 expression in macrophages, while over-expression of HIF-1alpha potentiated TLR4 expression. Chromatin immunoprecipitation assays revealed that HIF-1alpha binds to the TLR4 promoter region under hypoxic conditions. In addition, deletion or mutation of a putative HIF-1-binding motif in the TLR4 promoter greatly attenuated HIF-1alpha-induced TLR4 promoter reporter expression. Up-regulation of TLR4 expression by hypoxic stress enhanced the response of macrophages to lipopolysaccharide, resulting in increased expression of cyclooxygenase-2, interleukin-6, regulated on activation normal T cell expressed and secreted, and interferon-inducible protein-10. These results demonstrate that TLR4 expression in macrophages is up-regulated via HIF-1 in response to hypoxic stress, suggesting that hypoxic stress at sites of inflammation enhances susceptibility to subsequent infection and inflammatory signals by up-regulating TLR4.
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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.