Ventilation-induced neutrophil infiltration and apoptosis depend on apoptosis signal-regulated kinase 1 pathway*
Bibliographic record
Abstract
OBJECTIVE: Positive pressure ventilation with large tidal volumes has been shown to cause release of cytokines, including macrophage inflammatory protein (MIP)-2, a functional equivalent of human interleukin-8, neutrophil infiltration, and apoptosis. The mechanisms regulating ventilation-induced cytokine production and lung cell death are unclear. Based on our previous in vitro and in vivo models of lung cell stretch, we hypothesized that high tidal volume ventilation-induced MIP-2 production, neutrophil infiltration, and apoptosis are dependent on the activation of apoptosis signal-regulated kinase 1 (ASK1), the upstream activator of c-Jun N-terminal kinase (JNK). DESIGN: : Prospective, controlled animal experiment. SETTING: University research laboratory. SUBJECTS: Male C57BL/6 mice, weighting 20-25 g. INTERVENTIONS: C57BL/6 mice were exposed to high tidal volume (30 mL/kg) or low tidal volume (6 mL/kg) mechanical ventilation for 15 mins to 5 hrs. MEASUREMENTS AND MAIN RESULTS: High tidal volume ventilation induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apoptosis, and activation of ASK1, JNK, and activator protein (AP)-1 DNA binding in a dose-dependent and time-dependent manner. ASK1 inhibition with thioredoxin attenuated high tidal volume ventilation-induced MIP-2 messenger RNA expression, MIP-2 protein production, neutrophil migration into the lung, airway epithelial cell apoptosis, activation of JNK, and AP-1 DNA binding. CONCLUSIONS: Our data showed that high tidal volume ventilation-induced MIP-2 production, neutrophil sequestration, and apoptotic cell death were dependent, in part, on activation of the ASK1/JNK/AP-1 pathway.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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 source (direct Gemma or distilled Codex), 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".