title: PAR(2) expression in peripheral blood monocytes of patients with rheumatoid arthritis.
abstract: OBJECTIVE
  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.
authors.affiliation: School of Science, University of the West of Scotland, Paisley, UK.
authors.forename: A
authors.initials: A
authors.lastname: Crilly
authors.forename: E
authors.initials: E
authors.lastname: Burns
authors.forename: M B
authors.initials: MB
authors.lastname: Nickdel
authors.forename: J C
authors.initials: JC
authors.lastname: Lockhart
authors.forename: M E
authors.initials: ME
authors.lastname: Perry
authors.forename: P W
authors.initials: PW
authors.lastname: Ferrell
authors.forename: D
authors.initials: D
authors.lastname: Baxter
authors.forename: J
authors.initials: J
authors.lastname: Dale
authors.forename: L
authors.initials: L
authors.lastname: Dunning
authors.forename: H
authors.initials: H
authors.lastname: Wilson
authors.forename: J S
authors.initials: JS
authors.lastname: Nijjar
authors.forename: J A
authors.initials: JA
authors.lastname: Gracie
authors.forename: W R
authors.initials: WR
authors.lastname: Ferrell
authors.forename: I B
authors.initials: IB
authors.lastname: McInnes
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism; D017252:CD3 Complex / Q000378:metabolism; D002478:Cells, Cultured; D003430:Cross-Sectional Studies; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D017252:CD3 Complex; C508600:IL6 protein, human; D015850:Interleukin-6; D018950:Lipopolysaccharide Receptors; D044464:Receptor, PAR-2