Factors Regulating the Effect of IL-4 on Intestinal Epithelial Barrier Function
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Bibliographic record
Abstract
BACKGROUND: Inflammatory bowel disease is associated with an imbalance in cytokine production and defective intestinal barrier function. Previous studies indicate that IL-4, a cytokine increased in food allergy and in early Crohn's disease, enhances epithelial permeability. Here, we characterized the mechanism of action of IL-4 on cultured epithelial cells and examined if the anti-inflammatory cytokines, TGF-beta or IL-10, can modulate the effects of IL-4. METHODS: Confluent monolayers of human T84 epithelial cells were cultured with IL-4 alone or in combination with IL-10 or TGF-beta or with inhibitors of protein synthesis and blockers of IL-4 receptor signalling pathways. Permeability was evaluated by measuring transepithelial resistance (TER), flux of (3)H-fMLP (a small bacterial tripeptide) and horseradish peroxidase (HRP) (a macromolecule). RESULTS: T84 cells cultured with IL-4 showed a significant drop in TER as well as an increased flux of (3)H-fMLP and HRP. Co-treatment with IL-10 did not improve TER, whereas TGF-beta attenuated the resistance drop. However, neither TGF-beta nor IL-10 were able to correct the increased (3)H-fMLP flux. In contrast, the increased HRP flux caused by IL-4 was inhibited by both IL-10 and TGF-beta. TGF-beta and IL-10 significantly reduced IL-4-enhanced values for endosomal area and paracellular spaces containing HRP. Inhibitor studies indicated the requirement for protein synthesis and the involvement of phosphatidylinositol 3-kinase. CONCLUSIONS: These results provide new insights into the regulation of intestinal barrier function and may suggest a novel approach in the treatment of intestinal inflammation.
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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 | 0.001 |
| 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 it