Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall–induced arthritis
Article first published online: 30 SEP 2005
Copyright © 2005 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 52, Issue 10, pages 3239–3247, October 2005
How to Cite
Koenders, M. I., Kolls, J. K., Oppers-Walgreen, B., Van Den Bersselaar, L., Joosten, L. A. B., Schurr, J. R., Schwarzenberger, P., Van Den Berg, W. B. and Lubberts, E. (2005), Interleukin-17 receptor deficiency results in impaired synovial expression of interleukin-1 and matrix metalloproteinases 3, 9, and 13 and prevents cartilage destruction during chronic reactivated streptococcal cell wall–induced arthritis. Arthritis & Rheumatism, 52: 3239–3247. doi: 10.1002/art.21342
- Issue published online: 30 SEP 2005
- Article first published online: 30 SEP 2005
- Manuscript Accepted: 30 JUN 2005
- Manuscript Received: 29 APR 2004
- Dutch Arthritis Association. Grant Number: NR 00-1-302
- Veni Fellowship. Grant Number: 906-02-038
- The Netherlands Organization for Scientific Research. Grant Number: S95-384
To examine the role of interleukin-17 receptor (IL-17R) signaling in cartilage destruction and its interrelationship with synovial IL-1 expression during chronic reactivated streptococcal cell wall (SCW)–induced arthritis.
SCW arthritis was repeatedly induced in wild-type (WT) and IL-17R–deficient (IL-17R–/–) mice. At different time points, joint inflammation was assessed by using calipers to measure joint swelling. On day 42, mice were killed, and knee joints were removed for histologic analysis. Quantitative polymerase chain reaction (PCR) analyses for different proinflammatory mediators and matrix metalloproteinases (MMPs) were performed on inflamed synovium from WT and IL-17R–/– mice after 5 repeated injections of SCW fragments.
IL-17R signaling did not play a significant role in acute joint swelling induced by a single injection of SCW fragments directly into the joint. However, repeated local injections of SCW fragments into the knee joints of IL-17R–/– mice resulted in fewer infiltrating cells in the joint compared with WT mice. Moreover, histologic analysis on day 42 revealed a significant suppression of the degree of chondrocyte death and an absence of cartilage surface erosion in IL-17R–/– mice. Quantitative PCR analysis revealed impaired synovial expression of IL-1, IL-6, cyclooxygenase 2, stromelysin (MMP-3), gelatinase B (MMP-9), and collagenase 3 (MMP-13) in IL-17R–/– mice.
These data show a critical role of IL-17R signaling in driving the synovial expression of proinflammatory and catabolic mediators, such as IL-1 and different MMPs, during progression from an acute, macrophage-driven joint inflammation to a chronic, cartilage-destructive, T cell–mediated synovitis. Prevention of IL-17R signaling warrants consideration as a therapeutic target in chronic destructive arthritis.