Transcription factor decoy for NFκB inhibits cytokine and adhesion molecule expressions in synovial cells derived from rheumatoid arthritis

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Abstract
Objective. Numerous cytokines are expressed in lesions of synovial hyperplasia of patients with rheumatoid arthritis (RA), and their pathophysiological contributions have been the subject of speculation. These genes are regulated by the transcription factor NFκB which in turn is activated by tumour necrosis factor‐α (TNF‐α) and cytokines. In this study we examined the inhibition of the production of pro‐inflammatory cytokines, adhesion molecule and matrix metalloproteinase (MMP) from synovial tissue of patients with RA by the introduction of synthetic double‐stranded DNA with high affinity for the NFκB binding site. Method. NFκB decoy oligonucleotides (ODN) were introduced with the aid of the haemagglutinating virus of Japan (HVJ)–liposome method into synovial tissue or synovial cells derived from patients with RA. The levels of interleukin‐1β (IL‐1β), IL‐6, TNF‐α, intercellular adhesion molecule‐1 (ICAM‐1) and MMP‐1 were determined by means of enzyme‐linked immunosorbent assay (ELISA) and Northern blotting analysis. A cell counting kit was used to study the effect of NFκB decoy ODN on synovial cell proliferation. Results. The production of these mediators was significantly inhibited by the introduction of NFκB decoy ODN compared with the effect of scrambled decoy ODN. Transfection of NFκB decoy ODN resulted in a significant inhibition of synovial cell proliferation as compared with that of scrambled decoy ODN. Conclusion. The results demonstrated in this study suggest the potential usefulness of NFκB decoy ODN for gene therapy of inflammatory synovitis of RA.