In:
Arthritis & Rheumatism, Wiley, Vol. 60, No. 2 ( 2009-02), p. 396-407
Abstract:
Previously, we reported that interferon‐γ (IFNγ) aggravates cartilage destruction in immune complex (IC)–mediated arthritis via up‐regulation of activating Fcγ receptors (FcγR). Recently, we found that interleukin‐17 (IL‐17) also aggravates cartilage destruction in arthritis models in which ICs are involved, but the underlying mechanism remains unknown. This study was undertaken to determine the role of IL‐17 in FcγR‐mediated cartilage destruction in IC‐mediated arthritis and to compare its effect with that of IFNγ. Methods IC‐mediated arthritis was passively induced in γ‐chain −/− mice, which lack functional activating FcγR, and in wild‐type controls. AdIL‐17 or a control vector was injected into the knee joints 1 day prior to induction of IC‐mediated arthritis. Knee joints were isolated for histologic analysis, and synovium samples were obtained for reverse transcriptase–polymerase chain reaction (RT‐PCR). Macrophage (RAW 264.7) cell lines and polymorphonuclear cell (PMN; 32Dcl3) lines were stimulated with IFNγ or IL‐17 for analysis of FcγR expression using RT‐PCR and fluorescence‐activated cell sorting. Results IL‐17 overexpression prior to induction of IC‐mediated arthritis significantly aggravated cartilage destruction and inflammation, characterized by a massive influx of PMNs, which adhered to the cartilage surface. Although IL‐17 overexpression increased FcγR messenger RNA levels in the synovium, in vitro stimulation of macrophages and PMNs revealed that, in contrast to IFNγ, IL‐17 did not directly regulate FcγR expression. Despite similar inflammation in AdIL‐17–enhanced IC‐mediated arthritis in γ‐chain −/− mice and wild‐type controls, severe cartilage destruction and PMN adherence were completely absent in γ‐chain −/− mice. Conclusion Our findings indicate that IL‐17–mediated aggravation of cartilage destruction in IC‐mediated arthritis is FcγR dependent. However, in contrast to IFNγ, which directly up‐regulates FcγR expression on macrophages and PMNs, IL‐17 enhances cartilage destruction by increasing the local amount of FcγR‐bearing neutrophils.
Type of Medium:
Online Resource
ISSN:
0004-3591
,
1529-0131
Language:
English
Publisher:
Wiley
Publication Date:
2009
detail.hit.zdb_id:
2014367-9
detail.hit.zdb_id:
2754614-7
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