ERK Is Integral to the IFN-γ–Mediated Activation of STAT1, the Expression of Key Genes Implicated in Atherosclerosis, and the Uptake of Modified Lipoproteins by Human Macrophages
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
The proinflammatory cytokine IFN-gamma is a master regulator of atherosclerosis and mediates its cellular actions mainly through STAT1. Unfortunately, the impact of other IFN-gamma inducible pathways on STAT1 activation and the regulation of downstream responses associated with atherosclerosis in human macrophages are poorly understood and were therefore investigated. In this study, we demonstrate that the IFN-gamma-mediated phosphorylation of STAT1 on Ser(727), crucial for its maximal activity, was attenuated in human macrophages by pharmacological inhibition of ERK. In these cells, IFN-gamma induced changes in the expression of several key genes implicated in atherosclerosis, such as MCP-1, through an ERK-dependent mechanism. Additionally, the IFN-gamma-induced activity of STAT1-responsive promoters was attenuated by transfection of dominant-negative forms of ERK and other key components of this pathway. Furthermore, the IFN-gamma-induced uptake of acetylated and oxidized low-density lipoprotein by human macrophages was attenuated by pharmacological inhibition or RNA interference-mediated knockdown of ERK. These studies suggest a critical role for ERK signaling in the IFN-gamma-mediated changes in macrophage cholesterol homeostasis and gene expression during atherosclerosis.
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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 | 0.001 | 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 | 0.001 |
| 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 it