School of Science, University of the West of Scotland, Paisley, UK.
Ann Rheum Dis. 2012 Jun;71(6):1049-54. doi: 10.1136/annrheumdis-2011-200703. Epub 2012 Jan 30.
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.
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.
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).
These findings are consistent with a pathogenic role for PAR(2) in RA.
蛋白酶激活受体 2（PAR2）是一种 G 蛋白偶联受体，可被具有促炎活性的丝氨酸蛋白酶激活。本研究旨在探讨类风湿关节炎（RA）衍生白细胞亚群中 PAR2 表达的存在及其功能意义。
从 RA 和骨关节炎（OA）患者以及健康对照者中采集静脉血。通过流式细胞术分析外周血单核细胞（PBMCs）表面 PAR2 的表达，通过 ELISA 分析白细胞介素 6（IL-6）的生成。
与对照组相比，RA 患者 CD14+单核细胞表面 PAR2 的表达升高，但存在可变（中位数（第 1 至 3 四分位数）1.76%（0.86-4.10%）比 0.06%（0.03-0.81%），p<0.0001）。CD3+T 细胞表现出相似的模式，与对照组相比，RA 患者的 PAR2 表达明显更高（3.05%（0.36-11.82%）比 0.08%（0.02-0.28%），p<0.0001）。对于这两个亚群，PAR2 表达在疾病活动水平高的患者中显著升高（p<0.00001）：CD14+和 CD3+细胞的 PAR2 表达均与 C 反应蛋白和红细胞沉降率相关。此外，在一组新诊断的 RA 患者中，在接受甲氨蝶呤或柳氮磺胺吡啶治疗 3 个月后，CD14+和 CD3+细胞中升高的 PAR2 表达明显降低，这种降低与 28 关节疾病活动评分的降低显著相关（p<0.05）。OA 患者的细胞 PAR2 表达较低，与对照组相似。与 OA 患者和对照组相比，对选择性 PAR2 激动剂反应的单核细胞生成的 IL-6 显著增加（p<0.05）。
这些发现与 PAR2 在 RA 中的致病作用一致。
