Interleukin‐8 stimulates CFTR‐mediated mucus secretion by submucosal glands in swine (869.10)
Bibliographic record
Abstract
Cystic Fibrosis (CF) is an autosomal recessive condition caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane conductance Regulator (CFTR) anion channel. As a result epithelial fluid and ion transport is compromised. Many organs are affected in CF patients, but most of the mortality and morbidity arise from airway disease characterized by chronic infection and inflammation. However, the events leading from CFTR mutation to airway disease are not fully understood. Recent data suggest that abnormal bacteria clearance due to abnormal mucus secretion is the pathogenic event that triggers airway disease in CF. Thus we studied the response of airway epithelia to proinflammatory cytokines, such as Interleukin‐8 (IL‐8), that are released in response to bacterial infection and are elevated in CF airways. Secretion assays and electrophysiological techniques were used to measure the response of submucosal glands, the principal mucus source, to IL‐8. The mucus secretion rate increased from 0.052 to 0.156 nl/min upon the addition of IL‐8 (50 ng/ml). IL‐8 stimulated Na+ flux across the serous acini of the submucosal glands. Both effects were blocked by treatment with the CFTR inhibitor, CFTRinh172. Exposure to CFTRinh172 reduced IL‐8‐stimulated mucus secretion to 0.062 nl/min and abolished Na+ transport across the serous acini. Our results suggest that, in normal lungs, bacteria‐activated secretion increases mucus and bactericidal compounds in the airways, thereby facilitating bacterial removal by mucociliary clearance and reducing the proinflammatory stimulus. In CF airways, bacteria would activate proinflammatory signalling to trigger innate immune responses, but CFTR‐mediated mucus secretion and the resulting “bacterial flush” would be missing, leading to sustained inflammation that may permanently alter the physiology and anatomy of the airways. Grant Funding Source : Supported by APS, University of Saskatchewan, NSERC, Cystic Fibrosis Canada
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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 | 0.001 |
| 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 | 0.001 |
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".