| First Author | Ferrell WR | Year | 2003 |
| Journal | J Clin Invest | Volume | 111 |
| Issue | 1 | Pages | 35-41 |
| PubMed ID | 12511586 | Mgi Jnum | J:81119 |
| Mgi Id | MGI:2448097 | Doi | 10.1172/JCI16913 |
| Citation | Ferrell WR, et al. (2003) Essential role for proteinase-activated receptor-2 in arthritis. J Clin Invest 111(1):35-41 |
| abstractText | Using physiological, pharmacological, and gene disruption approaches, we demonstrate that proteinase-activated receptor-2 (PAR-2) plays a pivotal role in mediating chronic inflammation. Using an adjuvant monoarthritis model of chronic inflammation, joint swelling was substantially inhibited in PAR-2-deficient mice, being reduced by more than fourfold compared with wild-type mice, with virtually no histological evidence of joint damage. Mice heterozygous for PAR-2 gene disruption showed an intermediate phenotype. PAR-2 expression, normally limited to endothelial cells in small arterioles, was substantially upregulated 2 weeks after induction of inflammation, both in synovium and in other periarticular tissues. PAR-2 agonists showed potent proinflammatory effects as intra-articular injection of ASKH95, a novel synthetic PAR-2 agonist, induced prolonged joint swelling and synovial hyperemia. Given the absence of the chronic inflammatory response in the PAR-2-deficient mice, our findings demonstrate a key role for PAR-2 in mediating chronic inflammation, thereby identifying a novel and important therapeutic target for the management of chronic inflammatory diseases such as rheumatoid arthritis. |
