Rheumatology Advance Access published online on March 29, 2006
Rheumatology, doi:10.1093/rheumatology/kel078
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1 Department of Rheumatology, University Hospital of Wales, UK
* To whom correspondence should be addressed. Objectives. Despite recent major advances in the understanding of the pathogenesis of rheumatoid arthritis, with tumour necrosis factor-alpha (TNF Methods. Infection with reporter adenoviruses transferring the Results. The spontaneous production of macrophage-produced pro-inflammatory cytokines varied: TNF Conclusions. The OA synovium is a highly inflammatory environment, with spontaneous production of many cytokines and matrix metalloproteinases. Inhibition of NF
Received September 1, 2005
Accepted February 10, 2006
Original Papers
Adenoviral gene transfer into osteoarthritis synovial cells using the endogenous inhibitor I
N. Amos 1,
S. Lauder 2,
A. Evans 2,
M. Feldmann 3,
and
J. Bondeson 2 *
B
reveals that most, but not all, inflammatory and destructive mediators are NFB dependent
2 Department of Rheumatology, Cardiff University, Heath Park, Cardiff CF14 4XN, London W6 8LH, UK
3 Kennedy Institute of Rheumatology Division, Imperial College School of Medicine, 1 Aspenlea Road, Hammersmith, London W6 8LH, UK
J. Bondeson, E-mail: BondesonJ{at}cf.ac.uk
Abstract 
) established as a major therapeutic target, comparatively little is known about the mediators involved in the destructive and inflammatory pathways in osteoarthritis (OA). Recently, it has become appreciated that an inflammatory synovitis contributes not only to the signs and symptoms of osteoarthritis, but also to disease progression. Here, we use high-efficiency adenoviral gene transfer to investigate the role of the transcription factor nuclear factor-
B (NFB) in regulating inflammatory and destructive mediators in the late stage OA synovium.
-galactosidase or green fluorescent protein genes verified that OA synovial cells could be infected (>95%). Adenovirus transferring the inhibitory subunit IB inhibited NFB. The production of a whole array of pro- and anti-inflammatory cytokines and mediators, and several matrix metalloproteinases and their main inhibitor, was measured by enzyme-linked immunosorbent assay. was modestly inhibited by IB overexpression, but interleukin (IL)-1 was unaffected. Both IL-6 and IL-8 were potently inhibited, as were granulocyte-macrophage colony stimulating factor and oncostatin M. Anti-inflammatory mediators like IL-10, the IL-1 receptor antagonist and the p55 soluble TNF receptor were unaffected. Matrix metalloproteinases 1, 3, 9 and 13 were potently inhibited by IB overexpression, but not their main inhibitor tissue inhibitor of metalloproteinase-1.B may have a beneficial effect on the balance between pro-inflammatory cytokines and anti-inflammatory mediators, and between destructive metalloproteinases and their main inhibitor.
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