Determining the downstream signaling pathways through which prostaglandin E2 inhibits inflammatory mediator output in in human myometrial cells (911.6)
Bibliographic record
Abstract
Objective: Prostaglandin E2 (PGE2) represses interleukin‐1β (IL‐1β) induced inflammatory mediator output in human myometrial cells via EP2/4 receptors. Downstream EP2/4 signaling involves upregulation of intracellular cAMP which may activate multiple pathways, including protein kinase A (PKA) and exchange proteins activated by cAMP (Epacs). Methods: Myometrial biopsies from term elective Caesarean deliveries prior to labour onset (n=5, 37‐40 weeks gestation) were used to isolate myometrial cells. PKA and Epac gene expression was assessed by RT‐PCR. Myometrial cells were either non‐treated or stimulated with IL‐1β +/‐ co‐treatment with cAMP analogs to selectively activate PKAI, PKAII, or Epacs. Interleukin‐8 (CXCL8) output was measured by ELISA. Statistical analysis was performed by repeated measures ANOVA followed by a Bonferroni test. Results: Expression of both Epac isoforms and six of seven PKA subunits were identified in isolated myometrial cells. IL‐1β increased CXCL8 output in human myometrial cells (p蠄0.001). Co‐treatment with PKAI or PKAII selective cAMP analogs repressed this response (p蠄0.001). No significant repression was observed when cells were co‐treated with the Epac selective cAMP analog. Conclusions: PGE2 mediated repression of IL‐1β induced inflammatory output in human myometrial cells is mediated in part by PKA, but not Epac, signaling pathways. Grant Funding Source : Supported by Canadian Institutes of Health Research and Alberta Innovates‐Health Solutions
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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) | 0.003 | 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".