Protease-activated receptor-2 (PAR-2): a potential new target in arthritis

W.R. Ferrell, J.C. Lockhart, R.J. Plevin

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Protease-activated receptors (PARs) are a novel family of seven-transmembrane G-protein-coupled receptors. The unique feature of this family is that activation is initiated by cleavage of the N-terminus by serine or other proteases, thereby unmasking a tethered ligand that then interacts with the receptor, leading to activation. PARs have been described in the context of inflammation, and recent evidence indicates a particular role for the second member of this family, PAR-2, in arthritis. Synovial expression of this receptor is greatly upregulated in murine models of arthritis, and both acute and chronic experimental monoarthritis are substantially attenuated in Par2 knockout mice, suggesting a key role for PAR-2 in inflammatory joint disease. These findings translate to inflammatory disease in humans, since PAR-2 expression is upregulated in synovial tissues from patients with rheumatoid arthritis (RA), and appears to be an upstream regulator of proinflammatory cytokine generation, including tumor necrosis factor alpha (TNF-alpha). These findings identify PAR-2 as a new therapeutic target in the management of RA, and the challenge is now to develop potent and selective agents to prevent activation of this receptor.
Original languageEnglish
Pages (from-to)241-248
Number of pages7
JournalDrugs of the Future
Issue number3
Publication statusPublished - Mar 2008


  • arthritis
  • inflammatory joint disease
  • protease-activated receptor-2
  • PAR-2


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