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 journalArticle

2 Citations (Scopus)

Abstract

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.
LanguageEnglish
Pages241-248
Number of pages7
JournalDrugs of the Future
Volume33
Issue number3
DOIs
Publication statusPublished - Mar 2008

Fingerprint

PAR-2 Receptor
Arthritis
Proteinase-Activated Receptors
Rheumatoid Arthritis
Joint Diseases
Knockout Mice
Serine
Peptide Hydrolases
Tumor Necrosis Factor-alpha
Cytokines
Ligands
Inflammation

Keywords

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

Cite this

Ferrell, W.R. ; Lockhart, J.C. ; Plevin, R.J. / Protease-activated receptor-2 (PAR-2): a potential new target in arthritis. In: Drugs of the Future. 2008 ; Vol. 33, No. 3. pp. 241-248.
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Protease-activated receptor-2 (PAR-2): a potential new target in arthritis. / Ferrell, W.R.; Lockhart, J.C.; Plevin, R.J.

In: Drugs of the Future, Vol. 33, No. 3, 03.2008, p. 241-248.

Research output: Contribution to journalArticle

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