Protease-Activated Receptors Upregulate Cyclooxygenase-2 Expression in Human Endothelial Cells
Bibliographic record
Abstract
We have previously shown that the serine protease thrombin and other G protein-coupled agonists acutely enhance synthesis and release of prostacyclin from human umbilical vein endothelial cells (HUVEC) through activation of cPLA2 alpha. Here, we show that thrombin and other physiological endothelial cell agonists upregulate COX-2 induction in HUVEC. Thrombin treatment caused a rapid and sustained increase in prostacyclin (PGI2) synthesis from HUVEC. Thrombin and a selective protease-activated receptor-1 (PAR-1) peptide (TRAP) evoked dose- and time-dependent increases in COX-2 protein expression which were equivalent to that induced by the proinflammatory cytokine IL-1 alpha. Quantitative and real-time PCR analysis showed enhanced COX-2 mRNA expression in thrombin- or TRAP-stimulated HUVEC whereas COX-1 expression was unaffected. A PAR-2 agonist peptide also induced COX-2 protein and mRNA expression with kinetics distinct from those of thrombin, and promoted PGI2 release. These results demonstrate that regulation of COX-2 induction is an important functional response of HUVEC to PAR activation and suggest that PARs promote sustained upregulation of prostanoid production in human endothelium.
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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) | 0.002 | 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".