DEFICIENCY IN PROTEINASE-ACTIVATED RECEPTOR-2 (PAR2) ATTENUATES COLONIC INFLAMMATION IN MICE INDEPENDENT OF BONE MARROW DERIVEDCELLS.
Bibliographic record
Abstract
Background andaims: The role of PAR_2 duringintestinal inflammation is unclear, since its activation in the gut could lead to either pro- or anti-inflammatory properties. The aim of this study was to investigate the effects of PAR_2 deficiency (using PAR_2-deficient mice: PAR_2 ^-/-)in an animal model of colitis and to investigate the role of PAR_2 deficiency on bone marrow-derived cells. Methods: Colonic inflammation in PAR_2 ^+/+ and PAR_2 ^-/- mice was induced by 2.5 % dextran sodium sulfate(DSS). Chimeric mice (PAR_2^Ch+/+ or PAR_2^Ch-/-) injected with bone marrow cells (BMC) from either PAR_2 ^+/+ or PAR_2 ^-/- mice, were also given DSS. Results: PAR_2 ^+/+ mice treated with DSS showed a significant increase in leukocyte rolling/adherence, bowel thickness, myeloperoxidase (MPO) activity and macroscopic damage compared to PAR_2 ^-/-. PAR_2^Ch-/- mice, regardless of the source of bone marrow cells injected, showed significantly reduced inflammatory parameters, compared to PAR_2^Ch+/+ injected with PAR_2 ^+/+ bone marrow. A similar degree of DSS-induced inflammation was observed between chimeric PAR_2^Ch+/+ mice injected with either PAR_2 ^-/- or PAR_2 ^+/+bone marrow cells. Conclusions: Since DSS inflammation was reduced in PAR_2^ch-/- compared with PAR_2^ch+/+ mice, irrespective of the source of donor bone marrow cells, we conclude that PAR_2 expression on recipient tissues rather than on donor bone marrow cells plays a key role in the development and maintenance of DSS-induced colitis. PAR_2 thus appears as an important mediator of colonic inflammation and represents apotential target for the treatment of inflammatory bowel diseases. Supported by CIHR and the Crohn's and Colitis Foundation of Canada
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| 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".