Downregulation of ENaC expression and activity by <i>Pseudomonas</i> LPS in alveolar epithelial cells
Bibliographic record
Abstract
Pseudomonas aeruginosa is a gram negative bacteria that causes chronic infection in cystic fibrosis patients and is known to modulate the epithelial Na channel (ENaC) expression in experimental chronic pneumonia models. For this reason, we tested if LPS from P. aeruginosa could modulate the expression and activity of ENaC in alveolar epithelial cells. Alveolar epithelial cells purified from rat lung were cultured on permeable filters for 4 days before the cells were treated on the apical side with 15 μg/ml of Pseudomonas LPS. The treatment decreased gradually the total transepithelial current with the lowest point reached at 4h with a 35% decline compared to untreated cells. The ENaC (amiloride‐sensitive) portion of this current was declined by 53% at 4h. The α and βENaC mRNA were decreased respectively to 55% and 54% of control by a 4h LPS treatment. Estimation of ENaC activity at the apical membrane following amphotericin B permeabilisation of the basolateral membrane in presence of a Na gradient shows a 52% decrease in 4h LPS treated cells. The decline in ENaC current elicited by LPS is therefore the consequence of a decreased activity of the channel. Ro‐31 8820 a PKC inhibitor abolished the downregulation of ENaC activity in the cells and also restored the α and γENaC mRNA level back to normal. These results show that LPS downregulates ENaC mRNA expression and activity in alveolar epithelial cells by a PKC‐sensitive pathway. Supported by CCFF and CIHR
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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 | 0.000 | 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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 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".