Cloning, Expression, and Up-regulation of Inducible Rat Prostaglandin E Synthase during Lipopolysaccharide-induced Pyresis and Adjuvant-induced Arthritis
Bibliographic record
Abstract
We have cloned and expressed the inducible form of prostaglandin (PG) E synthase from rat and characterized its regulation of expression in several tissues after in vivo lipopoylsaccharide (LPS) challenge. The rat PGE synthase is 80% identical to the human enzyme at the amino acid level and catalyzes the conversion of PGH(2) to PGE(2) when overexpressed in Chinese hamster ovary K1 (CHO-K1) cells. PGE synthase activity was measured using [(3)H]PGH(2) as substrate and stannous chloride to terminate the reaction and convert all unreacted unstable PGH(2) to PGF(2alpha) before high pressure liquid chromatography analysis. We assessed the induction of PGE synthase in tissues from Harlan Sprague-Dawley rats after LPS-induced pyresis in vivo. Rat PGE synthase was up-regulated at the mRNA level in lung, colon, brain, heart, testis, spleen, and seminal vesicles. Cyclooxygenase (COX)-2 and interleukin 1beta were also up-regulated in these tissues, although to different extents than PGE synthase. PGE synthase and COX-2 were also up-regulated to the greatest extent in a rat model of adjuvant-induced arthritis. The RNA induction of PGE synthase in lung and the adjuvant-treated paw correlated with a 3.8- and 16-fold induction of protein seen in these tissues by immunoblot analysis. Because PGE synthase is a member of the membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG) family, of which leukotriene (LT) C(4) synthase and 5-lipoxygenase-activating protein are also members, we tested the effect of LTC(4) and the 5-lipoxygenase-activating protein inhibitor MK-886 on PGE synthase activity. LTC(4) and MK-886 were found to inhibit the activity with IC(50) values of 1.2 and 3.2 microm, respectively. The results demonstrate that PGE synthase is up-regulated in vivo after LPS or adjuvant administration and suggest that this is a key enzyme involved in the formation of PGE(2) in COX-2-mediated inflammatory and pyretic responses.
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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".