Crilly, A. et al. (2012) PAR2 expression in peripheral blood monocytes of patients with rheumatoid arthritis. Annals of the Rheumatic Diseases, 71 (6). pp. 1049-1054. ISSN 0003-4967 (doi:10.1136/annrheumdis-2011-200703)
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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 functio©nal 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.
|Glasgow Author(s):||McInnes, Prof Iain and Dale, Dr James and Gracie, Dr J Alastair and Ferrell, Prof William and Nijjar, Dr Jagtar|
|Authors:||Crilly, A., Burns, E., Nickdel, M.B., Lockhart, J.C., Perry, M.E., Ferrell, P.W., Baxter, D., Dale, J., Dunning, L., Wilson, H., Nijjar, J.S., Gracie, J.A., Ferrell, W.R., and McInnes, I.B.|
|College/School:||College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation|
|Journal Name:||Annals of the Rheumatic Diseases|
|Publisher:||B M J Group|
|Published Online:||30 January 2012|