tailieunhanh - Báo cáo y học: " Interferon-γ inhibits interleukin-1β-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học General Psychiatry cung cấp cho các bạn kiến thức về ngành y đề tài: Interferon-γ inhibits interleukin-1β-induced matrix metalloproteinase production by synovial fibroblasts and protects articular cartilage in early arthritis. | Page et al. Arthritis Research Therapy 2010 12 R49 http content 12 2 R49 RESEARCH ARTICLE Open Access Interferon-Y inhibits interleukin-ip-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 Williams 2 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-Y IFN-y during early inflammatory arthritis. Methods We studied IFN-y s capacity to modulate interleukin-1p IL-1P 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-y modulated IL-1P driven matrix metalloproteinases MMP synthesis resulting in the down-regulation of MMP-1 and MMP-3 production in vitro. IFN-y did not affect IL-1P 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-y reduced IL-1P expression in the arthritic joint and prevented cartilage degeneration on Day 3 of AIA. Conclusions Early therapeutic intervention with IFN-y may be critical to orchestrate tissue-protective responses during inflammatory arthritis. Introduction Interferon-y IFN-y is traditionally regarded as a proin-flammatory cytokine by virtue of its strong macrophageactivating 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