Dendritic Polyglycerol Sulfate Reduces Inflammation Through Inhibition of the HMGB1/RAGE Axis in RAW 264.7 Macrophages
Bibliographic record
Abstract
High Mobility Group Box 1 (HMGB1) is a central pro-inflammatory mediator released from damaged or stressed cells, where it activates receptors such as the Receptor for Advanced Glycation Endproducts (RAGE). Dendritic polyglycerol sulfate (dPGS), a hyperbranched polyanionic polymer, is known for its anti-inflammatory activity. In this study, we examined how dPGS modulates HMGB1-driven signaling in RAW 264.7 macrophages and human microglia. Recombinant human HMGB1 expressed in Escherichia coli (E. coli) was purified by nickel-nitrilotriacetic acid (Ni-NTA) and heparin chromatography. Proximity ligation assays (PLA) revealed that dPGS significantly disrupted HMGB1/RAGE interactions, particularly under lipopolysaccharide (LPS) stimulation, thereby reducing inflammatory signaling complex formation. This correlated with reduced activation of the nuclear factor kappa B (NF-κB) pathway, demonstrated by decreased nuclear translocation and transcriptional activity. Reverse transcription polymerase chain reaction (RT-PCR) and quantitative real-time PCR (RT-qPCR) showed that dPGS suppressed HMGB1- and LPS-induced transcription of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), monocyte chemoattractant protein-1 (MCP-1), cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Enzyme-linked immunosorbent assay (ELISA) and Griess assays confirmed reduced TNF-α secretion and nitric oxide production. Electron paramagnetic resonance (EPR) spectroscopy further showed that dPGS altered HMGB1/soluble RAGE (sRAGE) complex dynamics, providing mechanistic insight into its receptor-disruptive action.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".