Genomic and lipidomic analyses differentiate the compensatory roles of two COX isoforms during systemic inflammation in mice ,
Bibliographic record
Abstract
Both cyclooxygenase (COX)-1 and COX-2, encoded by Ptgs1 and Ptgs2 , function coordinately during inflammation. But the relative contributions and compensations of COX-1 and COX-2 to inflammatory responses remain unanswered. We used three engineered mouse lines where the Ptgs1 and Ptgs2 genes substitute for one another to discriminate the distinct roles and interchangeability of COX isoforms during systemic inflammation. In macrophages, kidneys, and lungs, "flipped" Ptgs genes generate a "reversed" COX expression pattern, where the knock-in COX-2 is expressed constitutively and the knock-in COX-1 is lipopolysaccharide inducible. A panel of eicosanoids detected in serum and kidney demonstrates that prostaglandin (PG) biosynthesis requires native COX-1 and cannot be rescued by the knock-in COX-2. Our data further reveal preferential compensation of COX isoforms for prostanoid production in macrophages and throughout the body, as reflected by urinary PG metabolites. NanoString analysis indicates that inflammatory networks can be maintained by isoform substitution in inflamed macrophages. However, COX-1>COX-2 macrophages show reduced activation of inflammatory signaling pathways, indicating that COX-1 may be replaced by COX-2 within this complex milieu, but not vice versa. Collectively, each COX isoform plays a distinct role subject to subcellular environment and tissue/cell-specific conditions, leading to subtle compensatory differences during systemic inflammation.
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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 | 0.001 | 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".