PI3K/Akt pathway contributes to development of apoptosis resistance during differentiation of human macrophages by maintaining antiapoptotic Bcl-xL protein expression (48.7)
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Bibliographic record
Abstract
Abstract Resistance to apoptosis is an important characteristic that human macrophages acquire during differentiation from monocytes. However, the intracellular mechanisms that mediate the development of resistance remain mostly unknown. We have used PMA-treated THP1 cells and MCSF-stimulated primary monocytes to generate human macrophages. By using chemical inhibitors for the PI3K and MAPK pathways, our results show that only pretreatment of cells before differentiation with the PI3K/Akt inhibitor LY294002 induced caspase dependent apoptosis that was associated with decreased expression of antiapoptotic Bcl-xL protein. These results were confirmed by inactivation of this pathway by Akt specific siRNAs. Moreover, this effect was specific if Akt was knocked down before inducing differentiation. Furthermore, Bcl-xL expression was found to be dependent on NFkB in differentiating macrophages. However, NFkB activation was prevented by LY294002 pretreatment, indicating that NFkB is responsible for Bcl-xL expression via PI3K/Akt signaling. Taken together, these results suggest that survival of macrophages is distinctly regulated during and after differentiation. A signaling pathway encompassing PI3K/Akt-mediated activation of NFkB plays a key role in survival of differentiating macrophages by specifically sustaining antiapoptotic Bcl-xL expression.
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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