Contribution of bone marrow-derived cells to the pro-inflammatory effects of protease-activated receptor-2 in colitis
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Bibliographic record
Abstract
OBJECTIVE: Our aim was to determine the contribution of proteinase-activated receptor-2 (PAR(2))-expressing bone marrow-derived cells on the development of colonic inflammation. MATERIALS: Chimeric mice were generated by injecting bone marrow cells from wildtype (PAR (2) (+/+) ) or PAR(2) knockout mice (PAR (2) (-/-) ) into irradiated PAR (2) (+/+) or PAR (2) (-/-) mice. TREATMENTS: Colitis was induced by giving 2.5% dextran sodium sulfate (DSS) solution for 7 days or by a single intracolonic administration of trinitrobenzene sulphonic acid (TNBS, 2 mg dissolved in 40% ethanol). METHODS: Seven days after the induction of colitis, bowel thickness, inflammatory parameters [myeloperoxidase (MPO) activity, macroscopic/microscopic damage scores], and leukocyte trafficking (visualized via intravital microscopy) were assessed. RESULTS: Total deficiency of PAR(2) resulted in a marked reduction in severity of both TNBS and DSS induced colitis as assessed by MPO activity, macroscopic damage, bowel thickness, and leukocyte adherence. Colitis was attenuated in all chimeric lines in which there was loss of PAR(2) in the host, non-bone marrow-derived tissue, independent of the status of PAR expression by bone marrow-derived cells. Interestingly, TNBS colitis was attenuated in PAR (2) (+/+) chimeric mice with PAR (2) (-/-) derived bone marrow but these animals were not protected from DSS colitis. CONCLUSIONS: Expression of PAR(2) by host-derived tissues plays a dominant role in regulating colonic inflammation. PAR(2) expression by bone marrow-derived cells appears to play a role in TNBS colitis but not in DSS induced injury.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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) | 0.000 | 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 it