title: Evaluation of protease-activated receptor 2 in murine models of arthritis.
abstract: OBJECTIVE
  Protease-activated receptor 2 (PAR-2) activation has been linked to pro- and antiinflammatory cellular responses. We undertook this study to explore the importance of PAR-2 activation in 4 murine models of arthritis and to analyze the expression of PAR-2 in human arthritic synovium.
  
  
  METHODS
  Zymosan-induced arthritis (ZIA), K/BxN serum-induced arthritis, and Freund's complete adjuvant (CFA)-induced arthritis were generated in naive PAR-2(-/-) mice and PAR-2(+/+) littermates. Antigen-induced arthritis (AIA) was generated in immunized mice using methylated bovine serum albumin (mBSA). The severity of arthritis was assessed by clinical scoring, technetium uptake measurement, and histologic analysis. Immune responses to mBSA were also evaluated from AIA. The expression of PAR-2 in synovial tissues from rheumatoid arthritis (RA) and osteoarthritis (OA) patients was compared.
  
  
  RESULTS
  In AIA, arthritis was significantly decreased in PAR-2-deficient mice and was associated with decreased levels of anti-mBSA IgG antibodies and lymph node cell proliferation. No difference in arthritis severity was seen in mice with ZIA, K/BxN serum-induced arthritis, and CFA-induced arthritis. Synovial biopsy specimens from RA patients demonstrated significantly increased expression of PAR-2 compared with those from OA patients.
  
  
  CONCLUSIONS
  PAR-2 deficiency was found to modulate articular inflammation in murine models of arthritis that require prior immunization and was associated with reduced levels of anti-mBSA IgG and lymph node cell proliferation in AIA. Expression of PAR-2 in RA synovium was significantly higher than that in OA synovium, and this suggests that PAR-2 is implicated in the pathogenesis of immune-mediated forms of arthritis.
authors.affiliation: Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Busso
authors.forename: Matthias
authors.initials: M
authors.lastname: Frasnelli
authors.forename: Roland
authors.initials: R
authors.lastname: Feifel
authors.forename: Bruno
authors.initials: B
authors.lastname: Cenni
authors.forename: Martin
authors.initials: M
authors.lastname: Steinhoff
authors.forename: Justin
authors.initials: J
authors.lastname: Hamilton
authors.forename: Alexander
authors.initials: A
authors.lastname: So
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D019085:Fluorescent Antibody Technique, Direct; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D018345:Mice, Knockout; D010003:Osteoarthritis / Q000378:metabolism / Q000473:pathology; D044464:Receptor, PAR-2 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D013583:Synovial Membrane / Q000378:metabolism* / Q000473:pathology
chemical_list: D044464:Receptor, PAR-2