ArticleBioscience reports2018
Hypoxia potentiates monocyte-derived dendritic cells for release of tumor necrosis factor α via MAP3K8.
Article in Bioscience reports, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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
22 citing papers in PubMed, 40 citations in OpenAlex.
- Analysis of the Expression Patterns of Tumor Necrosis Factor Alpha Signaling Pathways and Regulatory MicroRNAs in Astrocytic Tumors.International journal of molecular sciences · 2025Article
- Multiomics dissection of human RAG deficiency reveals distinctive patterns of immune dysregulation but a common inflammatory signature.Science immunology · 2025Article
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
- Expression and Regulation of Hypoxia-Inducible Factor Signalling in Acute Lung Inflammation.Cells · 2024Review
- Emerging roles of MITF as a crucial regulator of immunity.Experimental & molecular medicine · 2024Review
- The Application of Drugs and Nano-Therapies Targeting Immune Cells in Hypoxic Inflammation.International journal of nanomedicine · 2024Review
- Comparing the Blood Response to Hyperbaric Oxygen with High-Intensity Interval Training-A Crossover Study in Healthy Volunteers.Antioxidants (Basel, Switzerland) · 2023Article
- Hypoxia-inducing cryogels uncover key cancer-immune cell interactions in an oxygen-deficient tumor microenvironment.Bioactive materials · 2023Article
- Hypoxia-inducing cryogels uncover key cancer-immune cell interactions in an oxygen-deficient tumor microenvironment.bioRxiv : the preprint server for biology · 2023Article
- Crosstalk between hypoxic cellular micro-environment and the immune system: a potential therapeutic target for infectious diseases.Frontiers in immunology · 2023Article
- Biomaterial-assisted local oxygenation safeguards the prostimulatory phenotype and functions of human dendritic cells in hypoxia.Frontiers in immunology · 2023Article
- Nasal obstruction promotes alveolar bone destruction in the juvenile rat model.Journal of dental sciences · 2022Article
- MRTF may be the missing link in a multiscale mechanobiology approach toward macrophage dysfunction in space.Frontiers in cell and developmental biology · 2022Article
- New Druggable Targets for Rheumatoid Arthritis Based on Insights From Synovial Biology.Frontiers in immunology · 2022Review
- Multimodal analysis for humaniScience · 2021Article
- Metabolism of Dendritic Cells in Tumor Microenvironment: For Immunotherapy.Frontiers in immunology · 2021Review
- Network- and systems-based re-engineering of dendritic cells with non-coding RNAs for cancer immunotherapy.Theranostics · 2021Article
- Integrative Bioinformatics Analysis Reveals Potential Target Genes and TNFα Signaling Inhibition by Brazilin in Metastatic Breast Cancer Cells.Asian Pacific journal of cancer prevention : APJCP · 2020Article
- miR-21-5p Under-Expression in Patients with Obstructive Sleep Apnea Modulates Intermittent Hypoxia with Re-Oxygenation-Induced-Cell Apoptosis and Cytotoxicity by Targeting Pro-Inflammatory TNF-α-TLR4 Signaling.International journal of molecular sciences · 2020Article
- Radical Stress Is More Cytotoxic in the Nucleus than in Other Organelles.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Dendritic cells (DCs) constantly sample peripheral tissues for antigens, which are subsequently ingested to derive peptides for presentation to T cells in lymph nodes. To do so, DCs have to traverse many different tissues with varying oxygen tensions. Additionally, DCs are often exposed to low oxygen tensions in tumors, where vascularization is lacking, as well as in inflammatory foci, where oxygen is rapidly consumed by inflammatory cells during the respiratory burst. DCs respond to oxygen levels to tailor immune responses to such low-oxygen environments. In the present study, we identified a mechanism of hypoxia-mediated potentiation of release of tumor necrosis factor α (TNF-α), a pro-inflammatory cytokine with important roles in both anti-cancer immunity and autoimmune disease. We show in human monocyte-derived DCs (moDCs) that this potentiation is controlled exclusively via the p38/mitogen-activated protein kinase (MAPK) pathway. We identified MAPK kinase kinase 8 (MAP3K8) as a target gene of hypoxia-induced factor (HIF), a transcription factor controlled by oxygen tension, upstream of the p38/MAPK pathway. Hypoxia increased expression of MAP3K8 concomitant with the potentiation of TNF-α secretion. This potentiation was no longer observed upon siRNA silencing of MAP3K8 or with a small molecule inhibitor of this kinase, and this also decreased p38/MAPK phosphorylation. However, expression of DC maturation markers CD83, CD86, and HLA-DR were not changed by hypoxia. Since DCs play an important role in controlling T-cell activation and differentiation, our results provide novel insight in understanding T-cell responses in inflammation, cancer, autoimmune disease and other diseases where hypoxia is involved.
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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.