Treatment of Human T Cells with Bisperoxovanadium Phosphotyrosyl Phosphatase Inhibitors Leads to Activation of Cyclooxygenase-2 Gene
Bibliographic record
Abstract
Protein-tyrosine phosphatase (PTP) inhibitors are potent activators of T lymphocytes, most likely by affecting the early steps of T cell receptor (TCR) signaling. We have analyzed the effect of the PTP inhibitor bisperoxovanadium (bpV) on expression of the human cyclooxygenase 2 (COX-2) gene, which is induced following TCR triggering. Here we show that COX-2 promoter activity is markedly up-regulated following exposure of Jurkat T cells to bpV(pic). Interestingly enough, treatment of Jurkat cells with cyclic AMP-elevating agents such as forskolin, in combination with bpV, resulted in a more important COX-2 transcriptional activation. Such activation is inhibited by the immunosuppressive drugs FK506 and cyclosporin A. The two nuclear factor of activated T cells (NFAT) binding sites located within the COX-2 promoter region are involved in bpV-mediated positive effect on COX-2 promoter. Electromobility shift assays showed that NFAT1 and activator protein-1 are both translocated to the nucleus following bpV treatment. The active participation of p56(lck), ZAP-70, p36(LAT), and calcium in the bpV-dependent signaling cascade leading to COX-2 transcriptional activation was demonstrated using deficient cell lines and specific inhibitors. Although several PTPs are most likely targeted by bpV, our data suggest that the bpV-mediated signaling cascade is initiated by inhibition of SHP-1, which leads to phosphorylation of p56(lck) and ZAP-70 and, ultimately, to NFAT and activator protein-1 nuclear translocation. These results suggest that PTP inhibitors can activate COX-2 gene expression in a manner very similar to the stimulation induced by TCR triggering.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".