Syk mediates airway hyper-responsiveness and airway remodeling in a chronic mouse model of house dust mite induced allergic airways disease
Bibliographic record
Abstract
BACKGROUND: Asthma is characterized by airways hyper-responsiveness (AHR), chronic inflammation, remodeling and reversible obstruction. We have shown treatment with Syk (spleen tyrosine kinase) inhibitor to abrogate AHR to methacholine (MCh) in a mouse model of established ovalbumin-induced airways inflammation. The role of Syk in airway remodeling is not known. OBJECTIVE: To investigate the role of Syk in the pathogenesis of AHR and remodeling in a mouse model of allergic airways inflammation. METHODS: We used acute and chronic mouse models of house dust mite-induced (HDM; Dermatophagoides farina and D. pteronyssinus, respectively) airways inflammation. The role of Syk was investigated by pharmacological inhibition and in Syk flox/flox //rosa26CreER T2 conditional knockout mice. Respiratory mechanics and MCh-responsiveness were assessed using the flexiVent® system, and airway remodeling determined by semi-quantitative histological analysis. RESULTS: AHR in response to HDM was abrogated in the Syk knockout when compared with Syk-expressing mice. Similarly, AHR was reduced to control levels in response to a single dose of the Syk inhibitor, NVP-QAB-205, given intratracheally after establishment of allergic airways inflammation. Airways inflammation was not affected by either Syk knockout or NVP-QAB-205. Histological analysis indicated fibrosis, epithelial thickening, mucus cell hyperplasia and smooth muscle cell hypertrophy to be attenuated in the Syk knockout model when compared with Syk-expressing controls. CONCLUSIONS: These studies suggest that Syk mediates AHR and airway remodeling in a chronic model of allergen-induced airways inflammation.
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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) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 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 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".