The Ability of Serine Proteases to Induce an Increase in Barrier Function is Dependent on the Tight Junction Protein Occludin
Bibliographic record
Abstract
Inflammatory mediators disrupt the tight junction and may contribute to the pathogenesis of IBD through modulation of barrier function. We have found that serine proteases such as trypsin and matriptase induce an increase in barrier function in intestinal epithelial cell lines. However we do not know if they can reverse barrier disruption induced by inflammation, or how they modulate components of the tight junction (TJ). The SCBN canine epithelial cell line was mounted in Ussing chambers and barrier function assessed by 4 kDa FITC‐dextran flux and transepithelial electrical resistance (TER) measurement. Apical treatment with trypsin (45 BAU/mL) or matriptase (0.5 BAU/mL) induces a rapid and sustained increase in TER and decrease in FITC‐dextran flux. Treatment of cells with IFNγ and TNFα for 48 hours induced a dose‐dependent increase in permeability and redistribution of claudin‐4, tricellulin, and occludin from the TJ, as assessed by confocal immunofluorescence. The higher the doses of cytokines, the less able trypsin or matriptase could induce an increase in TER or decrease in FITC flux. Knockdown of occludin using siRNA resulted in a 39.8% reduction in baseline TER but no change in FITC‐dextran flux. Occludin knockdown induced a 74.1% and 90.6% reduction in the ability of trypsin and matriptase, respectively, to induce an increase in TER. Phosphorylation status of myosin light chain was assessed by Phos‐tag acrylamide Western blotting and no changes were observed with serine protease treatment. Thus, during inflammatory conditions, cytokines alter tight junctional structure and occludin localization; causing serine proteases to lose their ability to enhance epithelial barrier function.
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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 | 0.002 | 0.002 |
| 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".