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 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 | 0.000 | 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) | 0.000 | 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 itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, 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".