PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis

A Crilly1, E Burns, M B Nickdel

  • 1School of Science, University of the West of Scotland, Paisley, UK.

Abstract

Insights

Proteinase-activated receptor 2 (PAR(2)) is elevated on immune cells in rheumatoid arthritis (RA), correlating with disease activity. Treatment reduced PAR(2) expression, suggesting a role in RA pathogenesis.

Area of Science:

  • Immunology
  • Rheumatology
  • Cell Biology

Background:

  • Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor involved in inflammatory processes.
  • PAR(2) is activated by serine proteinases and has been implicated in various inflammatory conditions.

Purpose of the Study:

  • To investigate the expression and functional significance of PAR(2) on leukocyte subsets in rheumatoid arthritis (RA).
  • To determine if PAR(2) expression correlates with disease activity and treatment response in RA patients.

Main Methods:

  • Analysis of PAR(2) surface expression on peripheral blood mononuclear cells (PBMCs) using flow cytometry in patients with RA, osteoarthritis (OA), and healthy controls.
  • Measurement of interleukin-6 (IL-6) generation by monocytes in response to a PAR(2) agonist using ELISA.
  • Correlation of PAR(2) expression with disease activity markers (C-reactive protein, erythrocyte sedimentation rate) and treatment outcomes.

Main Results:

  • Elevated PAR(2) expression was observed on CD14+ monocytes and CD3+ T cells in RA patients compared to controls.
  • PAR(2) expression on these cells correlated significantly with disease activity markers and was reduced following treatment with methotrexate or sulfasalazine.
  • Monocytes from RA patients showed significantly greater IL-6 generation in response to a PAR(2) agonist compared to OA patients and controls.
  • PAR(2) expression on cells from OA patients was similar to control subjects.

Conclusions:

  • The findings suggest a pathogenic role for PAR(2) in rheumatoid arthritis.
  • PAR(2) expression on immune cells may serve as a biomarker for RA disease activity and treatment response.