| First Author | Seeliger S | Year | 2003 |
| Journal | FASEB J | Volume | 17 |
| Issue | 13 | Pages | 1871-85 |
| PubMed ID | 14519665 | Mgi Jnum | J:85990 |
| Mgi Id | MGI:2677646 | Doi | 10.1096/fj.02-1112com |
| Citation | Seeliger S, et al. (2003) Proinflammatory role of proteinase-activated receptor-2 in humans and mice during cutaneous inflammation in vivo. FASEB J 17(13):1871-85 |
| abstractText | 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-/-) 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. |
