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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.
Objectives:
Proteinase-activated receptor 2 (PAR(2)) is a G protein-coupled receptor activated by serine proteinases with proinflammatory activity. A study was undertaken to investigate the presence and functional significance of PAR(2) expression on rheumatoid arthritis (RA)-derived leucocyte subsets.
Methods:
Venous blood was obtained from patients with RA and osteoarthritis (OA) as well as healthy control subjects. Surface expression of PAR(2) on peripheral blood mononuclear cells (PBMCs) was analysed by flow cytometry and interleukin 6 (IL-6) generation by ELISA.
Results:
Patients with RA had elevated but variable surface expression of PAR(2) on CD14+ monocytes compared with control subjects (median (1st to 3rd quartiles) 1.76% (0.86-4.10%) vs 0.06% (0.03-0.81%), p<0.0001). CD3+ T cells showed a similar pattern with significantly higher PAR(2) expression in patients with RA compared with controls (3.05% (0.36-11.82%) vs 0.08% (0.02-0.28%), p<0.0001). For both subsets, PAR(2) expression was significantly higher (p<0.00001) in patients with high levels of disease activity: PAR(2) expression for both CD14+ and CD3+ cells correlated to C reactive protein and erythrocyte sedimentation rate. Furthermore, in a cohort of patients with newly diagnosed RA, elevated PAR(2) expression in both CD14+ and CD3+ cells was significantly reduced 3 months after methotrexate or sulfasalazine treatment and this reduction correlated significantly with the reduction in the 28-joint Disease Activity Scale score (p<0.05). PAR(2) expression on cells from patients with OA was low, similar to levels seen in control subjects. Generation of IL-6 by monocytes in response to a selective PAR(2) agonist was significantly greater in patients with RA than in patients with OA and control subjects (p<0.05).
Conclusions:
These findings are consistent with a pathogenic role for PAR(2) in RA.
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.
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