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Open Access Research article

Interferon-γ inhibits interleukin-1β-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis

Charlotte E Page1, Shaun Smale2, Sara M Carty2, Nicholas Amos1, Sarah N Lauder2, Rhian M Goodfellow2, Peter J Richards3, Simon A Jones3, Nicholas Topley3 and Anwen S Williams2*

Author Affiliations

1 Section of Rheumatology, University Hospital of Wales, Cardiff and Vale NHS Trust; Heath Park, Cardiff, Wales, CF14 4XW, UK

2 Section of Rheumatology, Department of Medicine, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, CF14 4XN, UK

3 Department of Infection, Immunity & Biochemistry, School of Medicine, Cardiff University, Heath Park, Cardiff, Wales, CF14 4XN, UK

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Arthritis Research & Therapy 2010, 12:R49  doi:10.1186/ar2960

Published: 22 March 2010

Abstract

Introduction

The first few months after symptom onset represents a pathologically distinct phase in rheumatoid arthritis (RA). We used relevant experimental models to define the pathological role of interferon-γ (IFN-γ) during early inflammatory arthritis.

Methods

We studied IFN-γ's capacity to modulate interleukin-1β (IL-1β) induced degenerative responses using RA fibroblast-like synoviocytes (FLS), a bovine articular cartilage explant (BACE)/RA-FLS co-culture model and an experimental inflammatory arthritis model (murine antigen-induced arthritis (AIA)).

Results

IFN-γ modulated IL-1β driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-γ did not affect IL-1β induced tissue inhibitor of metalloproteinase-1 (TIMP-1) production by RA FLS but skewed the MMP/TIMP-1 balance sufficiently to attenuate glycosaminoglycan-depletion in our BACE model. IFN-γ reduced IL-1β expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA.

Conclusions

Early therapeutic intervention with IFN-γ may be critical to orchestrate tissue-protective responses during inflammatory arthritis.