IL‐10 mitigates TNF‐alpha induced cardiomyocyte apoptosis: Role of mitogen‐activated protein kinases
Bibliographic record
Abstract
Our recent data suggested that IL‐10 modulates the TNF‐[alpha] induced oxidative stress in cardiomyocytes. However, intracellular signaling events responsible for this effect are not known. Present study investigates the role of p38 and ERK 1/2 MAP kinases in TNF‐[alpha] induced cardiomyocyte apoptosis and its modulation by IL‐10. Cardiomyocytes isolated from Sprague Dawley rats were exposed to TNF‐[alpha] (10ng/ml), IL‐10 (10ng/ml) and IL‐10+TNF‐[alpha] (ratio 1) for 4hrs. H2O2 (positive control) and antioxidant trolox (20 [mu]mol/L) were used to confirm the role of oxidative stress. H2O2 (100 [mu]Ì) increased oxidative stress and apoptosis, TNF‐[alpha] mimicked these effects. Exposure to TNF‐[alpha]increased ROS production, caused cell injury, increased the number of apoptotic cells and Bax/Bcl‐xl ratio. This change was associated with an increase in p38 and a decrease in ERK 1/2 phosphorylation. IL‐10 by itself had no effect on these MAP kinases, but it prevented TNF‐[alpha] induced changes. Trolox mitigated TNF‐[alpha] induced changes. Pre‐exposure of cells to p38 inhibitor SB‐203580, prevented TNF‐[alpha] induced changes. Inhibition of ERK pathway with PD98059 attenuated protective role of IL‐10 against TNF‐[alpha] induced apoptosis. Present data suggest the essential role of p38 and ERK 1/2 in TNF‐[alpha] induced cardiomyocyte apoptosis and its modulation by IL‐10 (supported by 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) | 0.001 | 0.001 |
| 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 | 0.001 |
| 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".