Proinflammatory role of proteinase‐activated receptor‐2 in humans and mice during cutaneous inflammation in vivo
Bibliographic record
Abstract
Proteinase‐activated receptor‐2 belongs to a new subfamily of G‐protein‐coupled receptors. Its precise role during inflammation and the underlying mechanisms is still unclear. Our study establishes that PAR‐2 plays a direct proinflammatory role during cutaneous inflammation in mice and humans in vivo. In a model of experimentally induced allergic (ACD) and toxic (ICD) contact dermatitis (CD) we show that ear swelling responses, plasma extravasation, and leucocyte adherence were significantly attenuated in PAR‐2 null mutant (PAR‐2 −7− ) mice compared with wild‐type (PAR‐2 +/+ ) mice, especially at early stages. The proinflammatory effects by PAR‐2 activation were significantly diminished using nitric oxide‐synthase inhibitors, while NF‐kappaB and neuropeptides appear to play a minor role in these mechanisms. PAR‐2‐mediated up‐regulation of E‐selectin and cell adhesion molecule ICAM‐1;enhanced plasma extravasation was observed in humans and mice and of interleukin‐6 in mice in vivo. Thus, PAR‐2 may be a beneficial therapeutic target for the treatment of inflammatory skin diseases.— Seeliger, S., Derian, C. K., Vergnolle, N., Bunnett, N. W., Nawroth, R., Schmelz, M., von der Weid, P.‐Y., Buddenkotte, J., Sunderko¨tter, C., Metze, D., Andrade‐ Gordon, P., Harms, E., Vestweber, D., Luger, T. A., Steinhoff, M. Proinflammatory role of proteinase‐activated receptor‐2 in humans and mice during cutaneous inflammation in vivo. FASEB J. 17, 1871–1885 (2003)
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".