ArticleBiochemical pharmacology2015
Toll-like receptor 4 signaling: A common pathway for interactions between prooxidants and extracellular disulfide high mobility group box 1 (HMGB1) protein-coupled activation.
Article in Biochemical pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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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
26 citing papers in PubMed, 36 citations in OpenAlex.
- miR-19a-3p and miR-19b-3p Promote Microglia Activation Associated With Neuroinflammation.Journal of neuroscience research · 2026Article
- TLR2 Activation Enhances Inflammatory Signaling and Accelerates Cyst Growth and Renal Fibrosis in Polycystic Kidney Disease Mice.International journal of molecular sciences · 2026Article
- The seminal plasma sTLR4/IL-1β ratio as an independent factor associated with sperm chromatin condensation defects.Frontiers in physiology · 2026Article
- Abietic Acid Induces DNA Damage and Cell Apoptosis in Lung Cancer Cells Through Targeting TOP2A.Biomolecules · 2025Article
- Activation of toll-like receptor 2 promotes the expression of inflammatory mediators and cell proliferation of human polycystic kidney disease cells.Cellular signalling · 2025Article
- Pathophysiological role of high mobility group box-1 signaling in neurodegenerative diseases.Inflammopharmacology · 2025Review
- In Vitro Anti-Inflammatory Study of Limonoids Isolated fromCurrent issues in molecular biology · 2024Article
- High mobility group box-1: a potential therapeutic target for allergic rhinitis.European journal of medical research · 2023Review
- RIPK1 and RIPK3 inhibitors: potential weapons against inflammation to treat diabetic complications.Frontiers in immunology · 2023Review
- HMGB1 is a Potential and Challenging Therapeutic Target for Parkinson's Disease.Cellular and molecular neurobiology · 2023Review
- The Association between High Mobility Group Box 1 and Stroke-Associated Pneumonia in Acute Ischemic Stroke Patients.Brain sciences · 2022Article
- Extracellular Nucleophosmin Is Increased in Psoriasis and Correlates With the Determinants of Cardiovascular Diseases.Frontiers in cardiovascular medicine · 2022Article
- Doxorubicin induces an alarmin-like TLR4-dependent autocrine/paracrine action of Nucleophosmin in human cardiac mesenchymal progenitor cells.BMC biology · 2021Article
- Class IIa HDAC Downregulation Contributes to Surgery-Induced Cognitive Impairment Through HMGB1-Mediated Inflammatory Response in the Hippocampi of Aged Mice.Journal of inflammation research · 2021Article
- Quercetin Reduces Oxidative Stress and Apoptosis by Inhibiting HMGB1 and Its Translocation, Thereby Alleviating Liver Injury in ACLF Rats.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Comprehensive Analysis of a ceRNA Network Identifies lncR-C3orf35 Associated with Poor Prognosis in Osteosarcoma.BioMed research international · 2020Article
- Quercetin Attenuates d-GaLN-Induced L02 Cell Damage by Suppressing Oxidative Stress and Mitochondrial ApoptosisFrontiers in pharmacology · 2020Article
- HBx inhibits HMGB1 expression and active oxygen production in LO2 cells through the NF-κB signaling pathway.The Kaohsiung journal of medical sciences · 2019Article
- The molecular landscape of histone lysine methyltransferases and demethylases in non-small cell lung cancer.International journal of medical sciences · 2019Article
- DNA damage and apoptosis induced by a potent orally podophyllotoxin derivative in breast cancer.Cell communication and signaling : CCS · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Necrotic cells passively release HMGB1, which can stimulate TLR4 in an autocrine fashion to potentially initiate "sterile" inflammation that maintains different disease states. We have shown that prooxidants can induce NF-κB activation through TLR4 stimulation. We examined whether prooxidants enhance HMGB1-induced TLR4 signaling through NF-κB activation. We used LPS-EK as a specific agonist for TLR4, and PPC and SIN-1 as in situ sources for ROS. As model systems, we used HEK-Blue cells (stably transfected with mouse TLR4), RAW-Blue™ cells (derived from murine RAW 264.7 macrophages) and primary murine macrophages from TLR4-KO mice. Both HEK-Blue and RAW-Blue 264.7 cells express optimized secreted embryonic alkaline phosphatase (SEAP) reporter under the control of a promoter inducible by NF-κB. We treated cells with HMGB1 alone and/or in conjunction with prooxidants and/or inhibitors using SEAP release as a measure of TLR4 stimulation. HMGB1 alone and/or in conjunction with prooxidants increased TNFα and IL-6 released from TLR4-WT, but not from TLR4-KO macrophages. Pro-oxidants increased HMGB1 release, which we quantified by ELISA. We used both fluorescence microscopy imaging and flow cytometry to quantify the expression of intracellular ROS. TLR4-neutralizing antibody decreased prooxidant-induced HMGB1 release. Prooxidants promoted HMGB1-induced NF-κB activation as determined by increased release of SEAP and TNF-α, and accumulation of iROS. HMGB1 (Box A), anti-HMGB1 and anti-TLR4-neutralizing pAbs inhibited HMGB1-induced NF-κB activation, but HMGB1 (Box A) and anti-HMGB1 pAb had no effect on prooxidant-induced SEAP release. The present results confirm that prooxidants enhance proinflammatory effects of HMGB1 by activating NF-κB through TLR4 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.