Role of Transient receptor potential vanilloid 4 in neutrophil activation and acute lung injury
Bibliographic record
Abstract
Introduction Transient receptor potential vanilloid 4 (TRPV4) is a cation channel expressed in lung parenchyma and inflammatory cells. TRP channels have been implicated in the activation of inflammatory cells and the pathogenesis of acute lung injury (ALI), thus we hypothesized that TRPV4 deficiency or inhibition may attenuate inflammatory responses and ALI. Method To test this, in vivo and ex vivo studies were performed using TRPV4 −/− mice. Results Genetic deficiency or pharmacologic inhibition of TRPV4 attenuated the functional, histological and inflammatory hallmarks of ALI following intratracheal instillation of hydrochloric acid or lipopolysaccharide (LPS). TRPV4 −/− compared to TRPV4 +/+ mice had an increased survival rate following i.p. LPS. Perfused lung studies showed decreased lung weight increase in TRPV4 −/− mice in response to platelet activating factor (PAF). Transfusion of TRPV4 +/+ vs. TRPV4 −/− blood into perfused lungs led to greater Evans blue extravasation following PAF administration. Neutrophils from TRPV4 −/− mice had attenuated increases in intracellular calcium and reactive oxygen species and showed reduced endothelial transmigration in response to PAF. Conclusion Our findings identify a role for TRPV4 in neutrophil activation, and suggest TRPV4 as a promising pharmacological target for the prevention and potentially treatment of ALI. Supported by CREMS, University of Toronto and NSFC # 81000028
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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) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 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".