Modulation of lipopolysaccharide-induced NF-IL6 activation by protein kinase C-α in a mouse macrophage cell line
Bibliographic record
Abstract
We have previously shown that overexpression of a dominant-negative (DN) mutant of protein kinase C-alpha (PKC-alpha) in RAW 264.7 macrophages inhibited lipopolysaccharide (LPS)-induced IL-1alpha, inducible nitric oxide synthase and cyclooxygenase-2 expression. This inhibition was not related to defective NF-kappaB nuclear translocation, suggesting that PKC-alpha might be involved in the modulation of other LPS-inducible transcription factors. In the present study, we have investigated the impact of PKC-alpha on the activation of AP-1 and NF-IL6 in LPS-treated RAW 264.7 macrophages. Electrophoretic mobility shift assays and luciferase reporter constructs revealed that LPS-induced AP-1 transcriptional activity was normal in DN PKC-alpha-overexpressing RAW 264.7 cells. In contrast, LPS-induced DNA-binding and transcriptional activities of NF-IL6 were inhibited in DN PKC-alpha-overexpressing RAW 264.7 cells and correlated with an impairment of NF-IL6 nuclear translocation. Conversely, overexpression of either wild-type PKC-alpha or a constitutively active PKC-alpha mutant significantly enhanced LPS-stimulated NF-IL6-dependent promoter activity. Finally, LPS-induced expression of two genes regulated by NF-IL6, namely IL-1beta and granulocyte colony-stimulating factor, was impaired in DN PKC-alpha-overexpressing RAW 264.7 cells. Taken together, these results suggest that regulation of NF-IL6 activity constitutes one of the mechanisms by which PKC-alpha modulates LPS-induced gene expression in the mouse macrophage cell line RAW 264.7.
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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) | 0.001 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".