ET <sub>B</sub> receptor deficiency amplifies allergic airway inflammation and hyperresponsiveness
Bibliographic record
Abstract
Background Endothelin-1 (ET-1) is a proinflammatory mediator that plays a crucial role in regulating airway tone by activating G protein-coupled endothelin receptors A (ET A ) and B (ET B ). The endothelin system has been linked to asthma, but the impact of ET B receptor deficiency on allergic airway inflammation remains uncharted. This study explores how the endothelin system influences allergic airway inflammation and hyperresponsiveness. Methods We used rescued ET B receptor-deficient (ET B −/− ) mice to obviate lethal inherited Hirschsprung disease, prepro-ET-1 overexpressing ( pre ET tg ), and wild-type (WT) mice. Basal airway resistance and responsiveness to broncho-constrictive stimuli were assessed in isolated, perfused and ventilated lungs of naïve mice. Additionally, we analysed the humoral immune response and airway hyperresponsiveness following induction of type 2 airway inflammation induced by systemic ovalbumin (OVA) sensitisation and repeated airway challenge with aerosolised OVA. Results Naïve ET B −/− mice exhibited significantly heightened airway responsiveness compared to naïve WT mice. After OVA sensitisation and challenge, ET B −/− mice displayed increased OVA-specific immunoglobulin E levels, intensified allergic airway inflammation and hyperresponsiveness compared to WT mice. Conversely, pre ET tg mice displayed reduced immunoglobulin E levels, airway inflammation and hyperresponsiveness. Conclusion Our findings suggest ET B receptors have a protective role in asthma-associated allergic airway inflammation and hyperresponsiveness. The increased asthma phenotype in sensitised and challenged ET B −/− mice is attributed to ET B -specific immunomodulatory mechanisms, rather than to elevated levels of ET-1 resulting from impaired ET B -mediated ET-1 clearance. This conclusion is supported by the diminished asthma-phenotype observed in sensitised and challenged pre ET tg mice. Therefore, adjusting endothelin signalling could offer a promising approach to managing asthma.
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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 | 0.008 | 0.005 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".