ArticleInflammation2023
Hypoxia and TNF-α Synergistically Induce Expression of IL-6 and IL-8 in Human Fibroblast-like Synoviocytes via Enhancing TAK1/NF-κB/HIF-1α Signaling.
Article in Inflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- GV effects of diabetes mellitus on clinical outcomes of patients with acute heart failure: A systematic review and meta-analysis.PloS one · 2025Pooled it
- Study on the mechanism of Fuzi Lizhong decoction in the treatment of colorectal cancer of spleen kidney deficiency from the perspective of intestinal flora and hypoxia inducible factor-1α signalling pathway.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2025Trial
- Hypoxia as an amplifier of synovial inflammation in rheumatoid arthritis.Nature reviews. Rheumatology · 2026Review
- Hypoxia-inducible factor-1 (HIF-1) in the molecular mechanisms of liver fibrosis: research progress on its role and therapeutic strategies.Journal of applied genetics · 2026Review
- TNFα drives disease-specific chemokine networks and orbital tissue remodeling in a preclinical model of thyroid eye disease.European thyroid journal · 2026Article
- Smart colorimetric wound dressing for real-time infection detection and monitoring.Journal of biological engineering · 2026Review
- Metabolic and neuroimmune control of rheumatoid arthritis: therapeutic implications of FXR and α7-nAChR axes.Inflammopharmacology · 2026Review
- Soluble factors released from fibroblast-like synoviocytes of JIA patients with future extended course can condition persistent JIA synovial fibroblasts for increased IL-6 production.Arthritis research & therapy · 2026Article
- Targeting inflammatory microenvironments: overcoming therapy resistance and immunosuppression.Molecular cancer · 2026Review
- Hypoxia-Inducible Factors in Rheumatoid Arthritis: Central Pathogenic Roles and Therapeutic Opportunities.Journal of inflammation research · 2026Review
- MiR-129-5p is associated with chronic obstructive pulmonary disease status and alleviates cigarette smoke extract-induced human bronchial epithelial cell injury.Tobacco induced diseases · 2026Article
- Succinate-mediated metabolic alterations and signaling in RA: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- Histidine alleviates copper-induced intestinal inflammation through oxidative stress-mediated mitochondrial damage and the Hif1α-Tnfα/Il1β pathway.Frontiers in immunology · 2026Article
- High-altitude thrombosis: divergent pathophysiological mechanisms and preventive strategies in acutely exposed population and native highlanders.Frontiers in cardiovascular medicine · 2026Review
- HIF-1α: a bridge connecting sepsis and acute respiratory distress syndrome.European journal of medical research · 2025Review
- Hypoxia-Induced Inflammation in In Vitro Model of Human Blood-Brain Barrier: Modulatory Effects of the Olfactory Ensheathing Cell-Conditioned Medium.Molecular neurobiology · 2025Article
- Stabilization Splint Therapy for Patients with Temporomandibular Disorders Improves Opening Movements and Jaw Limitation and Attenuates Pain by Influencing the Levels of IL-7, IL-8, and IL-13 in the Gingival Crevicular Fluid.Medicina (Kaunas, Lithuania) · 2025Article
- Organ preservation: current limitations and optimization approaches.Frontiers in medicine · 2025Review
- The molecular interplay among gut dysbiosis, adipose tissue, and metabolite-derived damage-associated molecular patterns in metainflammation and atherogenesis.Frontiers in immunology · 2025Review
- The role of hypoxic microenvironment in rheumatoid arthritis.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia and increased levels of inflammatory cytokines in the joints are characteristics of rheumatoid arthritis (RA). However, the effects of hypoxia and tumor necrosis factor-α (TNF-α) on interleukin (IL)-6 and IL-8 production on fibroblast-like synoviocytes (FLSs) remain to be clarified. This study aimed to explore how hypoxia and TNF-α affect the expression of IL-6 and IL-8 in human FLSs isolated from RA patients. Hypoxia or TNF-α treatment alone significantly increased the expression and promoter activity of IL-6, IL-8, and hypoxia-inducible factor-1α (HIF-1α). Treatment of hypoxic FLSs with TNF-α further significantly elevated the expression of these cytokines and enhanced promoter activity of HIF-1α, which was abrogated by treatment with the HIF-1α inhibitor YC-1. Similarly, TNF-α alone elevated the phosphorylation and promoter activity of nuclear factor-κBp65 (NF-κBp65) in the FLSs. These effects were further enhanced by the combined treatment of hypoxia and TNFα but were attenuated by the NF-κB inhibitor BAY11-7082. NF-κB-p65 inhibition decreased the effect of TNF-α on HIF-1α upregulation in the FLSs in response to hypoxia. The combination of hypoxia and TNF-α also significantly upregulated transforming growth factor-β-activated kinase 1 (TAK1) expression, and silencing TAK1 dramatically decreased NF-κB-p65, HIF-1α, IL-6, and IL-8 expression under the same conditions. Our results indicate that hypoxia and TNF-α synergistically increase IL-6 and IL-8 expression in human FLSs via enhancing TAK1/NF-κB/HIF-1α signaling.
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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.