Role of protein tyrosine phosphatases in the regulation of interferon-γ-induced macrophage nitric oxide generation: implication of ERK pathway and AP-1 activation
Bibliographic record
Abstract
NO is a potent molecule involved in the cytotoxic events mediated by macrophages (MØ) against microorganisms. We reported previously that inhibition of MØ protein tyrosine phosphatases (PTPs) mediates a protective effect against Leishmania infection, which was NO-dependent. Herein, we show that the PTP inhibitors of the peroxovanadium (pV) class, bpV(phen) and bpV(pic), can similarly increase murine MØ IFN-gamma-induced NO generation. Using various second messenger (JAK2, MEK, Erk1/Erk2, and p38) antagonists, we found that the Erk1/Erk2 pathway was the principal pathway submitted to regulation by PTPs in the context of IFN-gamma-driven MØ activation and increase in NO production. We observed that bpV(phen) increases inducible NO synthase (iNOS) expression, resulting in enhanced NO production, whereas the bpV(pic) increase of NO production does not seem to result from a modulation of iNOS expression. Transcription factors STAT-1alpha and NF-kappaB, recognized for their importance in NO generation, were not affected by the pV treatment. However, AP-1 was strongly activated by bpV(phen) but not by bpV(pic). Collectively, our results suggest that increased IFN-gamma-induced NO production, observed after bpV(phen) treatment, involves the activation of the transcription factor AP-1 by Erk1/Erk2- and stress-activated protein kinase/JNK-dependent transduction mechanisms.
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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".