The therapeutic potential of proteinase-activated receptors in arthritis

Kathryn A McIntosh, Robin Plevin, William R Ferrell, John C Lockhart

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Proteinase-activated receptors are a family of seven-transmembrane G-protein-coupled receptors. Activation of PARs is initiated through cleavage of the N-terminus, unmasking a tethered ligand that can then interact with the receptor and lead to its activation. PARs exhibit both anti- and pro-inflammatory properties, although recent evidence has pointed towards a detrimental role for PARs, particularly PAR-2, in arthritis. Initial research using PAR-2 knockout mice identified PAR-2 as a key mediator of chronic joint inflammation. Further research examined the role of PAR-2 in human articular cell types, demonstrating upregulation of PAR-2 in cells from an inflammatory background compared with non-inflammatory cells, with PAR-2 levels being further upregulated by pro-inflammatory cytokines and growth factors. To date, there is no clinical evidence of a role for PAR-2 in vivo in humans, although recent studies utilizing human joint tissue and articular cells are emerging.

Original languageEnglish
Pages (from-to)334-338
Number of pages5
JournalCurrent Opinion in Pharmacology
Volume7
Issue number3
Early online date21 Mar 2007
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Proteinase-Activated Receptors
Arthritis
Joints
Therapeutics
Research
Knockout Mice
Intercellular Signaling Peptides and Proteins
Anti-Inflammatory Agents
Up-Regulation
Cytokines
Ligands
Inflammation

Keywords

  • animals
  • arthritis
  • humans
  • joints
  • receptor, PAR-2

Cite this

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title = "The therapeutic potential of proteinase-activated receptors in arthritis",
abstract = "Proteinase-activated receptors are a family of seven-transmembrane G-protein-coupled receptors. Activation of PARs is initiated through cleavage of the N-terminus, unmasking a tethered ligand that can then interact with the receptor and lead to its activation. PARs exhibit both anti- and pro-inflammatory properties, although recent evidence has pointed towards a detrimental role for PARs, particularly PAR-2, in arthritis. Initial research using PAR-2 knockout mice identified PAR-2 as a key mediator of chronic joint inflammation. Further research examined the role of PAR-2 in human articular cell types, demonstrating upregulation of PAR-2 in cells from an inflammatory background compared with non-inflammatory cells, with PAR-2 levels being further upregulated by pro-inflammatory cytokines and growth factors. To date, there is no clinical evidence of a role for PAR-2 in vivo in humans, although recent studies utilizing human joint tissue and articular cells are emerging.",
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The therapeutic potential of proteinase-activated receptors in arthritis. / McIntosh, Kathryn A; Plevin, Robin; Ferrell, William R; Lockhart, John C.

In: Current Opinion in Pharmacology, Vol. 7, No. 3, 06.2007, p. 334-338.

Research output: Contribution to journalArticle

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AU - Plevin, Robin

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AU - Lockhart, John C

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