A19 INTERLEUKIN-6 AND INTERLEUKIN-22 MEDIATE DISTICT REGULATION OF MITOCHONDRIAL DYNAMICS IN PATHOBIONT INFECTED GUT EPITHELIA
Bibliographic record
Abstract
Abstract Background The IBD-associated pathobiont attaching-invading Escherichia coli (AIEC) strain LF82 induces mitochondrial fragmentation and depolarization in epithelial cells, resulting in impaired ATP production and reduced barrier function. Interleukin (IL)-6 and IL-22 are omnipresent in the inflamed gut, can directly affect epithelial function and both mobilize STAT-3, the serine727 phosphorylated form of which can translocate to mitochondria. Thus, we posed the question, will IL-6 or IL-22 rescue or exaggerate the mitochondrial damage evoked by exposure to E. coli-LF82? Aims 1. To determine if IL-6 and IL-22 modulate mitochondrial function during E. coli-LF82 infection 2. To assess the mechanisms by which IL-6 and IL-22 affect mitochondrial function in model gut epithelia Methods Human colon-derived T84 epithelial cells were infected with E. coli-LF82 (108 CFU/mL, 4h) ± a 18h pre-treatment and then co-treatment with IL-6 or IL-22 (both 10 ng/mL). Bacterial internalization was evaluated, and mitochondrial network morphology visualized with MitoTracker Red and confocal microscopy. Mitochondrial membrane potential was evaluated using TMRE staining and flow cytometry, and ATP measured by a luminescence assay. STAT3 phosphorylation (S727 and Y705) in whole-cell extracts was determined via western blot in response to IL-6 or IL-22 during E. coli-LF82 infection. Results IL-6 inhibited E. coli-LF82 evoked mitochondrial fragmentation, with significantly more cells showing a fused tubular pattern: mitochondrial membrane potential was restored by ~50% and ATP depletion was less severe (n=5). IL-6 elicited increased pS727-STAT3. In contrast, IL-22 failed to prevent any of the mitochondrial changes caused by E. coli-LF82, did not cause increased pS727-STAT3 but bioactivity was confirmed by increased pY705-STAT3. IL-6, but not IL-22, reduced the number of viable intracellular bacteria without affecting bacterial growth and increased markers of autophagy activation. Conclusions We have uncovered divergent effects of the STAT3 activators, IL-6 and IL-22, in the control of epithelial mitochondrial dynamics and function when challenged with a bacterial pathobiont. We speculate that IL-6 limits the effects of E. coli-LF82 via mitochondrially-directed pS727-STAT3 signaling and upregulation of autophagy. Understanding the precise role of STAT3- activating cytokines signaling in mitochondrial regulation could reveal new target to enhance epithelial barrier function. Funding Agencies CIHR
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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 | 0.000 |
| 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) | 0.002 | 0.001 |
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".