Drs. Feifel and Cenni own stock and/or hold stock options in Novartis Pharma. Dr. So has received consulting fees and/or honoraria (less than $10,000 each) from Abbott Laboratories and Pfizer.
Evaluation of protease-activated receptor 2 in murine models of arthritis
Version of Record online: 28 DEC 2006
Copyright © 2006 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 56, Issue 1, pages 101–107, January 2007
How to Cite
Busso, N., Frasnelli, M., Feifel, R., Cenni, B., Steinhoff, M., Hamilton, J. and So, A. (2007), Evaluation of protease-activated receptor 2 in murine models of arthritis. Arthritis & Rheumatism, 56: 101–107. doi: 10.1002/art.22312
- Issue online: 2 JAN 2007
- Version of Record online: 28 DEC 2006
- Manuscript Accepted: 29 SEP 2006
- Manuscript Received: 10 MAY 2006
- Swiss National Scientific Research Fund. Grant Number: 3200-067231.01
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.
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.
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.
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.