Cutting Edge: TLR4 Deficiency Confers Susceptibility to Lethal Oxidant Lung Injury
Bibliographic record
Abstract
TLRs have been studied extensively in pathogen-mediated host responses. We use a murine model of lethal oxidant-mediated injury to demonstrate for the first time that mammalian TLR4 is required for survival and lung integrity. Administering high levels of inspired oxygen, or hyperoxia, is commonly used as a life-sustaining measure in critically ill patients. However, prolonged exposures can lead to respiratory failure and death. TLR4-deficient mice exhibited increased mortality and lung injury during hyperoxia. The enhanced susceptibility of TLR4-deficient mice to hyperoxia was associated with an inability to up-regulate Bcl-2 and phospho-Akt. Restoration of Bcl-2 and phospho-Akt levels by the exogenous transfer of the antioxidant gene heme oxygenase-1 markedly attenuated hyperoxia-induced injury, apoptosis, and mortality in TLR4-deficient mice. Taken together, our results suggest a protective role of TLR4 in oxidant-mediated injury, providing novel mechanistic links among innate immunity, oxidant stress, and apoptosis.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.008 | 0.001 |
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".