Propofol significantly attenuates iNOS, CAT-2, and CAT-2B transcription in lipopolysaccharide-stimulated murine macrophages.
Bibliographic record
Abstract
BACKGROUND: Propofol significantly inhibits inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) biosynthesis in stimulated macrophages. L-arginine transport mediated by the isozymes of type-2 cationic amino acid transporter (including CAT-2 and CAT-2B) has been reported to play a crucial role in regulating iNOS activity. We sought to evaluate the effects of propofol on L-arginine transport and transcription of CAT-2 and CAT-2B. METHODS: Confluent murine macrophages (RAW264.7 cells) were stimulated with lipopolysaccharide (LPS) to induce NO production, L-arginine transport and the transcriptions of iNOS, CAT-2, and CAT-2B. Propofol (25, 50, and 75 microM) was added to the cells 4 hours before, immediately after, or 4 hours after LPS administration. After reacting with LPS for 18 hours, cell cultures were harvested and assayed. RESULTS: Propofol administered 4 hours before LPS had no significant effects on NO production, L-arginine transport, and the transcriptions of iNOS and CAT-2. To our surprise, NO production and iNOS transcription were significantly enhanced by 25 microM propofol administered immediately after LPS. NO production and iNOS transcription were not affected by 50 microM propofol but significantly inhibited by 75 microM propofol administered immediately after LPS. CAT-2 transcription and L-arginine transport were significantly inhibited by 50 and 75 microM but not 25 microM propofol administered immediately after LPS. When administered 4 hours after LPS, 75 but not 25 and 50 microM propofol significantly inhibited NO production, L-arginine transport, and the transcription of iNOS and CAT-2. In addition, CAT-2B transcription was significantly inhibited by propofol that was administered 4 hours before, immediately after, or 4 hours after LPS. CONCLUSIONS: Propofol had significantly inhibitory effects on LPS-induced NO production, L-arginine transport, and the expressions of iNOS, CAT-2 and CAT-2B in stimulated murine macrophages in a dose-dependent manner. In addition, timing of administration also affected this regulatory effect of propofol.
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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 | 0.000 |
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".