Valproic acid suppresses interleukin‐1β‐induced microsomal prostaglandin E2 Synthase‐1 expression in chondrocytes
Bibliographic record
Abstract
INTRODUCTION Microsomal prostaglandin E2 Synthase (mPGES)‐1 catalyzes the terminal step in the biosynthesis of PGE2. Early growth response factor‐1 (Egr‐1) is a key transcription factor in the regulation of mPGES‐1. In the present study we examined the effects of valproic acid (VA), a histone deacetylase (HDAC) inhibitor, on interleukin (IL)‐1β‐induced mPGES‐1‐expression in human chondrocytes. METHODS Chondrocytes were stimulated with IL‐1 in the absence or presence of VA, and the level of mPGES‐1 protein and mRNA expression were evaluated using Western blotting and real‐time reverse‐transcription polymerase chain reaction, respectively. The mPGES‐1 promoter activity was analyzed in transient transfection experiments. Egr‐1 recruitment to the mPGES‐1 promoter were evaluated using chromatin immunoprecipitation (ChIP) assays. RESULTS VA dose‐dependently suppressed IL‐1β‐induced mPGES‐1 protein and mRNA expression as well as its promoter activation. Treatment with VA did not alter IL‐1‐induced Egr‐1 expression, nor its recruitment to the mPGES‐1 promoter, but prevented its transcriptional activity. CONCLUSION Our study demonstrates that VA inhibits IL‐1‐induced mPGES‐1 expression in chondrocytes. The suppressive effect of VA was not due to reduced expression or recruitment of Egr‐1 to the mPGES‐1 promoter.
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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) | 0.001 | 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 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".