Zonulin antagonist protects against tight junction disruption by <i>Pseudomonas aeruginosa</i> in airway epithelial cells
Bibliographic record
Abstract
Zonulin is known as a regulator of barrier function in both epithelial and endothelial cells in the intestine and kidney by acting through EGFR (epidermal growth factor receptor) and PAR2 (Proteinase activated receptors) to cause the dissociation of ZO‐1 from occludin and claudin‐1 from the cell junctions. Respiratory infection is characterized by increased lung permeability caused by the reduction in the abundance and/or distribution of proteins at the tight junction. Here the effect of the zonulin antagonist, larazotide acetate (LA) on airway epithelial cell barrier function after the addition of lipopolysaccharide (LPS) from Pseudomonas aeruginosa or undiluted P.aeruginosa filtrate isolated from an overnight culture was investigated. Two human airway epithelial cell models were used, H441 cells grown at air‐liquid interface and 16HBE14o‐cells grown as submerged monolayers. Cells were incubated with 10 μg/ml LPS and 12 mM larazotide acetate. Transepithelial electrical resistance (TEER) and permeability was measured after 1h and 6h. TEER was decreased with LPS which was prevented by LA, (p<0.05, n=3) LPS vs LPS/LA at 1 hour. Permeability was increased with LPS after 6h (p<0.05, n=3) LPS vs control. Cells were immunostained for ZO‐1 and E‐cadherin, LPS caused the disappearance of ZO‐1 staining at the apical surface which was conserved with LA. E‐cadherin localization did not change with either LPS or LPS/LA treatment. Total protein abundance assessed by western blot showed no changes. Exposure of 16HBE14o‐ cells to P.aeruginosa filtrate for 24 h lead to a 61% decrease in TEER compared to control (p<0.0001, n=3). P.aeruginosa filtrate/LA increased TEER by 39% (p<0.02, n=3). Tight junction localization of E‐cadherin and claudin‐1 were both disrupted with P.aeruginosa filtrate while incubation with LA attenuated this rearrangement. This study shows that larazotide acetate helped to counteract the damage to tight junctions caused by LPS and P.aeruginosa filtrate, this supports a role for zonulin as a regulator of lung epithelial barrier function. Support or Funding Information Funded by Astra Zeneca
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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 | 0.001 | 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) | 0.000 | 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".