%0 Journal Article
%T Interferon-¦Ă inhibits interleukin-1¦Â-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis
%A Charlotte E Page
%A Shaun Smale
%A Sara M Carty
%A Nicholas Amos
%A Sarah N Lauder
%A Rhian M Goodfellow
%A Peter J Richards
%A Simon A Jones
%A Nicholas Topley
%A Anwen S Williams
%J Arthritis Research & Therapy
%D 2010
%I BioMed Central
%R 10.1186/ar2960
%X We studied IFN-¦Ă's capacity to modulate interleukin-1¦Â (IL-1¦Â) 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)).IFN-¦Ă modulated IL-1¦Â driven matrix metalloproteinases (MMP) synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-¦Ă did not affect IL-1¦Â 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-¦Ă reduced IL-1¦Â expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA.Early therapeutic intervention with IFN-¦Ă may be critical to orchestrate tissue-protective responses during inflammatory arthritis.Interferon-¦Ă (IFN-¦Ă) is traditionally regarded as a proinflammatory cytokine by virtue of its strong macrophage-activating potential and its association with Th1 driven immune responses. This view is predominantly derived from in vitro observations at the cellular level. This belief has no doubt also contributed to our over-simplified understanding of major human autoimmune disorders such as rheumatoid arthritis (RA), multiple sclerosis and insulin-dependent diabetes mellitus and guided the development of therapeutic strategies for these diseases for over two decades. Accumulating contradictory findings from several in vivo experimental models of disease [1-7] as well as the suppressive role of IFN-¦Ă upon interleukin-17 [8] signifies a need to rethink the doctrine of proinflammatory and disease-enforcing function for IFN-¦Ă in autoimmune diseases such as RA.The strong protective role for IFN-¦Ă is exemplified in experimental models of arthritis, whereby genetic disruption of the IFN-¦Ă receptor or IFN-¦Ă results in increased disease activity [5-7]. In humans also a key immuno-modulatory function
%U http://arthritis-research.com/content/12/2/R49