Par-2 in the pathogenesis of collagen-induced arthritis: crucial role in T cell differentiation

M.B. Nickdel, H.S. Palmer, W.R. Ferrell, J.C. Lockhart, R.J. Plevin, I.B. McInnes

Research output: Contribution to journalArticle

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Abstract

Protease-activated receptor-2 (PAR-2) is a member of a novel family of seven-transmembrane G-protein-coupled receptors (PARs) activated by proteolytic cleavage to reveal a tethered ligand. Serine proteases such as mast cell tryptase cleave PAR-2 at a specific site within the extracellular N-terminus to expose a new N-terminal tethered ligand domain, which binds to and thereby activates the cleaved receptor. We previously demonstrated that adjuvant monoarthritis is substantially inhibited in PAR-2 'knockout' mice (1). The present study extended these earlier finding by investigating the therapeutic potential of a novel PAR-2 antagonist, ENMD-1068, in the murine model of collagen-induced arthritis (CIA); we recently demonstrated this antagonist inhibited TNF generation from the synovial membrane of RA patients (2). We further tested the hypothesis that this receptor contributes to the pathogenesis of arthritis by affecting T lymphocyte activation and/or differentiation to Th1, Th2 and Th17 phenotypes.
LanguageEnglish
PagesII54-II54
JournalRheumatology
Volume47
Issue numberSupplement 2
DOIs
Publication statusPublished - Apr 2008

Fingerprint

PAR-2 Receptor
Experimental Arthritis
Cell Differentiation
T-Lymphocytes
Ligands
Synovial Membrane
Serine Proteases
Knockout Mice
Arthritis
Phenotype

Keywords

  • collagen-induced arthritis
  • t cell differentiation
  • arthritis

Cite this

Nickdel, M. B., Palmer, H. S., Ferrell, W. R., Lockhart, J. C., Plevin, R. J., & McInnes, I. B. (2008). Par-2 in the pathogenesis of collagen-induced arthritis: crucial role in T cell differentiation. Rheumatology, 47(Supplement 2), II54-II54. https://doi.org/10.1093/rheumatology/kem514
Nickdel, M.B. ; Palmer, H.S. ; Ferrell, W.R. ; Lockhart, J.C. ; Plevin, R.J. ; McInnes, I.B. / Par-2 in the pathogenesis of collagen-induced arthritis: crucial role in T cell differentiation. In: Rheumatology. 2008 ; Vol. 47, No. Supplement 2. pp. II54-II54.
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Nickdel, MB, Palmer, HS, Ferrell, WR, Lockhart, JC, Plevin, RJ & McInnes, IB 2008, 'Par-2 in the pathogenesis of collagen-induced arthritis: crucial role in T cell differentiation' Rheumatology, vol. 47, no. Supplement 2, pp. II54-II54. https://doi.org/10.1093/rheumatology/kem514

Par-2 in the pathogenesis of collagen-induced arthritis: crucial role in T cell differentiation. / Nickdel, M.B.; Palmer, H.S.; Ferrell, W.R.; Lockhart, J.C.; Plevin, R.J.; McInnes, I.B.

In: Rheumatology, Vol. 47, No. Supplement 2, 04.2008, p. II54-II54.

Research output: Contribution to journalArticle

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