Examining the role of arginase in air pollution-induced exacerbation of asthma
Bibliographic record
Abstract
The arginase isozymes (arginase 1 and 2), convert L-arginine into L-ornithine and urea, and thus compete with the nitric oxide synthase isozymes for substrate. We have previously shown that arginase 1 expression is upregulated in human asthma and plays a functional role in airways hyperresponsiveness (AHR) in an animal model of allergic airways inflammation. Ambient particles and ozone are major constituents of urban air pollution and contribute to asthma exacerbations. However, the mechanisms underlying the exacerbation of allergic airways disease by air pollution remain to be elucidated. There is evidence that arginase expression is augmented in cigarette smoking asthmatics. We tested the hypothesis that arginase is involved in the exacerbation of respiratory symptoms in response to air pollution in animal models of allergic airways inflammation. We used sub-acute (16-day) and chronic (12-week) murine models of ovalbumin (OVA)-induced allergic airways inflammation as models of asthma. All mice were sensitized to OVA, and then randomized to aerosol challenge with PBS (control; OVA/PBS) or OVA (allergic airways inflammation; OVA/OVA). Twenty-four hours after the final OVA or PBS challenge, mice underwent a combined exposure to concentrated ambient fine particles plus ozone (CAP+O 3 ), or filtered air. Following exposure, mice were treated with either the arginase inhibitor S -boronoethyl l-cysteine (BEC; 40 μg/g b.w.), or vehicle (PBS), by direct nebulization into the airways. After determination of the airways responsiveness to methacholine using the flexiVent, tissues were harvested for Western blotting, activity testing and immunohistochemistry. Exposure to CAP+O 3 augmented the AHR in the OVA/OVA mice with no significant effect on the OVA/PBS controls in both the sub-acute and chronic models. Expression of arginase 1 and total arginase activity were significantly augmented in OVA/OVA mice exposed to CAP+O 3 , compared to filtered air. Immunohistochemistry revealed that arginase 1 expression was specifically up-regulated in the peribronchiolar region following CAP+O 3 exposure in OVA/OVA mice. Treatment with BEC significantly reduced the pollution-induced AHR in CAP+O 3 -exposed OVA/OVA mice in both the sub-acute and chronic murine models to control levels. This study demonstrates that arginase 1 is up-regulated following environmental exposures in murine models of allergic airways inflammation. Attenuation of airways hyperresponsiveness by arginase inhibition suggests that this pathway is a promising candidate for future therapies to prevent or treat air pollution-induced exacerbation of allergic symptoms.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".