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

Objective. Numerous cytokines are expressed in lesions of synovial hyperpla sia of patients with rheumatoid arthritis (RA)I and their pathophysiologica l contributions have been the subject of speculation. These genes are regul ated by the transcription factor NF kappa B which in turn is activated by t umour necrosis factor-alpha. (TNF-alpha) and cytokines. In this study we ex amined the inhibition of the production of pro-inflammatory cytokines, adhe sion molecule and matrix metalloproteinase (MMP) from synovial tissue of pa tients with RA by the introduction of synthetic double-stranded DNA with hi gh affinity for the NF kappa B binding site. Method. NF kappa B decoy oligonucleotides (ODN) were introduced with the ai d of the haemagglutinating virus of Japan (HVJ)-liposome method into synovi al tissue or synovial cells derived from patients with RA. The levels of in terleukin-1 beta (IL-1 beta), IL-6, TNF-alpha, intercellular adhesion molec ule-1 (ICAM-1) and MMP-1 were determined by means of enzyme-linked immunoso rbent assay (ELISA) and Northern blotting analysis. A cell counting kit was used to study the effect of NF kappa B decoy ODN on synovial cell prolifer ation. Results. The production of these mediators was significantly inhibited by t he introduction of NF kappa B decoy ODN compared with the effect of scrambl ed decoy ODN. Transfection of NF kappa B decoy ODN resulted in a significan t inhibition of synovial cell proliferation as compared with that of scramb led decoy ODN. Conclusion. The results demonstrated in this study suggest the potential us efulness of NF kappa B decoy ODN for gene therapy of inflammatory synovitis of RA.