ArticleJournal of molecular medicine (Berlin, Germany)2012
Involvement of TNFα-induced TLR4-NF-κB and TLR4-HIF-1α feed-forward loops in the regulation of inflammatory responses in glioma.
Article in Journal of molecular medicine (Berlin, Germany), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 84 citations in OpenAlex.
- Melatonin exerts anOncology letters · 2026Article
- Myrtenol modulates TWEAK/TLR4-NF-κB, miR-21, PTEN, and ERK-1 expressions and improves behavioral outcomes in a rat glioblastoma model.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Tumor-intrinsic TLR4 signaling as a context-dependent rheostat in glioblastoma.Journal of molecular medicine (Berlin, Germany) · 2026Review
- Neuroprotective effects of piracetam in vascular dementia: a review of toll-like receptor 4 -mediated neuroinflammatory pathways.Inflammopharmacology · 2026Review
- Antibiotics modulate Escherichia coli-derived bacterial extracellular vesicle production and their upregulation of ICAM-1 in human endothelial cells.Biology open · 2026Article
- Elucidating the association between TLR-4 expression and the clinical course of glioblastoma leptomeningeal disease.British journal of cancer · 2025Article
- Advances on the therapeutic potential of cell receptor activation in glioblastoma.Molecular biology reports · 2025Review
- Kinin BInflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Dysregulation of inflammasome activation in glioma.Cell communication and signaling : CCS · 2023Review
- Inflammation Regulation by Bacterial Molecular Patterns.Biomedicines · 2023Article
- Interleukin-6 and Hypoxia Synergistically Promote EMT-Mediated Invasion in Epithelial Ovarian Cancer via the IL-6/STAT3/HIF-1Analytical cellular pathology (Amsterdam) · 2023Article
- Review
- Immunogenic cell death related risk model to delineate ferroptosis pathway and predict immunotherapy response of patients with GBM.Frontiers in immunology · 2022Article
- Toll-like receptors and toll-like receptor-targeted immunotherapy against glioma.Journal of hematology & oncology · 2021Review
- Review
- Late p65 nuclear translocation in glioblastoma cells indicates non-canonical TLR4 signaling and activation of DNA repair genes.Scientific reports · 2021Article
- Differential Expression of theFrontiers in cell and developmental biology · 2021Article
- Characterization of dysregulated glutamine metabolism in human glioma tissue withScientific reports · 2020Article
- High TLR4 expression predicts a poor prognosis after esophagectomy for advanced thoracic esophageal squamous cell carcinoma.Esophagus : official journal of the Japan Esophageal Society · 2020Article
- TLR-4 Signaling vs. Immune Checkpoints, miRNAs Molecules, Cancer Stem Cells, and Wingless-Signaling Interplay in Glioblastoma Multiforme-Future Perspectives.International journal of molecular sciences · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The precise role of different toll-like receptor (TLR) superfamily members is just beginning to get elucidated in glioblastoma multiforme (GBM). In this study, we observed heightened TLR4 levels in GBM tumor samples as compared to adjacent normal tissue. Since the pro-inflammatory cytokine tumor necrosis factor (TNF)α induces NF-κB activation in GBM, and as several common signaling mediators are involved in TNFα and TLR4-mediated NF-κB activation, we investigated the role of TLR4 in the regulation of NF-κB activation and inflammatory responses in TNFα-treated glioma cells. TNFα elevated TLR4 expression and inhibition of TLR4 signaling by either signaling inhibitor, neutralizing antibody, or small interfering RNA (siRNA)-attenuated TNFα-induced NF-κB activation. TLR4-mediated NF-κB activation was independent of canonical myeloid differentiation factor 88 signaling but involved toll/IL-1R homology domain-containing adaptor protein-inducing interferon-β. Inhibition of TLR4 signaling abrogated TNFα-induced increase in (1) transcription factors interferon (IFN) regulatory factor 3 and STAT-1 and (2) IFNβ and inflammatory cytokines/chemokines expression. Furthermore, TNFα-induced TLR4-dependent increase in AKT activation and HIF-1α transcriptional activation suggested the existence of TLR4-AKT-HIF-1α axis. Importantly, TNFα-induced TLR4 was abrogated in cells transfected with dominant negative IκB and HIF-1α siRNA. Our studies indicate that TNFα triggered TLR4-HIF-1α and NF-κB-TLR4 feed-forward loops act in tandem to sustain inflammatory response in glioma.
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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.