Proton pump inhibitors reduce interferon‐γ‐induced neurotoxicity and STAT3 phosphorylation of human astrocytes
Bibliographic record
Abstract
Proton pump inhibitors (PPIs) are known to possess anti-inflammatory properties. Inflammatory processes, including astrocytic activation, are implicated in the pathogenesis of different neurodegenerative diseases. Our recent study has indicated that interferon (IFN)-γ-induced astrocytic neurotoxicity is mediated, at least in part, by phosphorylation of signal transducer and activator of transcription (STAT) 3. We therefore studied the effects of PPIs on IFN-γ-induced neurotoxicity and STAT3 activation of human astrocytes. Both lansoprazole (LPZ) and omeprazole (OPZ) significantly attenuated IFN-γ-induced neurotoxicity of human astrocytes and astrocytoma cells. These drugs inhibited IFN-γ-induced phosphorylation of STAT 3, but not STAT1. We found that LPZ significantly reduced secretion of IFN-γ-inducible T cell α chemoattractant from IFN-γ-activated astrocytes. Neither LPZ nor OPZ suppressed expression of intercellular adhesion molecule-1 by IFN-γ-activated astrocytes. These results suggest that PPIs attenuate IFN-γ-induced neurotoxicity of human astrocytes through inhibition of the STAT3 signaling pathway. PPIs that possess antineurotoxic properties may be a useful treatment option for Alzheimer's disease and other neuroinflammatory disorders associated with activated astrocytes.
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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 | 0.000 | 0.000 |
| 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 | 0.000 | 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".