Cigarette smoke stimulates cystic fibrosis transmembrane conductance regulator (CFTR) function in airway epithelial cells
Bibliographic record
Abstract
Cystic Fibrosis is a disease caused by genetic mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) channel resulting in dysfunctional chloride ion transport.Clinical manifestations of the disease include pancreatic fibrosis, malnutrition, and most importantly, failure of the mucociliary clearance.Drug intervention have significantly improved the quality and prognosis for CF patients.However, disease severity remains quite variable from patientto-patient.For instance, exposures to air pollutants, such as cigarette smoke, can significantly affect the outcome of CF patients.Although epidemiological and clinical studies have shown adverse effects of second-hand smoke exposure on CFTR function, the molecular mechanism by which smoke exposure alters CFTR activity remains obscure.In this study, we investigate passive smoke effects on WT-CFTR and corrected F508del-CFTR.Consistent with previous reports, exposure to 30% CSE for 1 h suppressed the subsequent stimulation of short circuit current (Isc) by forskolin, resulting in a decrease in CFTR function.Notably, corrected F508del-CFTR was found to be more sensitive to smoke than WT-CFTR.In addition to inhibiting the forskolin response, CSE exposure also caused a large, transient increase in basal Isc which was absent when cells were pretreated with CFTRinh-172 and when CFBE cells expressing F508del CFTR were exposed to CSE.This transient stimulation was blocked by H89 (a PKA inhibitor) and NS398 (a cAMP inhibitor), suggesting that this activation was cAMP-dependent protein kinase activation.Hydrogen peroxide has been shown previously to stimulate CFTR function, primarily through the autocrine signaling pathway prostaglandin E2 binding primarily to the prostaglandin type E4 receptor to initiate the activation of CFTR.Since cigarette smoke contains oxidants, we first explored the role of reactive oxygen species by pre-treating cells with Nacetylcysteine (NAC).The stimulation by CSE was strongly attenuated after 10mM NAC,
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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 | 0.001 | 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".