Rheumatology 2000; 39: 749-757
© 2000 British Society for Rheumatology
Transcription factor decoy for NF
B inhibits cytokine and adhesion molecule expressions in synovial cells derived from rheumatoid arthritis
Department of Orthopaedic Surgery,
1 Department of Geriatric Medicine,
2 Department of Gene Therapy Science, Osaka University Medical School,2-2 Yamada-oka, Suita 565-0871, Japan
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 NF
B which in turn is activated by tumour necrosis factor-
(TNF-) 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 NFB binding site.
Method. NFB 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-1ß (IL-1ß), IL-6, TNF-, 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 NFB decoy ODN on synovial cell proliferation.
Results. The production of these mediators was significantly inhibited by the introduction of NFB decoy ODN compared with the effect of scrambled decoy ODN. Transfection of NFB 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 NFB decoy ODN for gene therapy of inflammatory synovitis of RA.
KEY WORDS: Transcription factor decoy, Gene therapy, Rheumatoid arthritis, HVJ-liposome, Synovial cells.
Correspondence to: T. Tomita, Department of Orthopaedic Surgery, Osaka University Medical School, 2-2 Yamada-oka, Suita, Osaka 565-0871, Japan.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Bene, R. C. Kurten, and T. C. Chambers Subcellular localization as a limiting factor for utilization of decoy oligonucleotides Nucleic Acids Res., October 21, 2004; 32(19): e142 - e142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B Safieh-Garabedian, G M Mouneimne, W El-Jouni, M Khattar, and R Talhouk The effect of endotoxin on functional parameters of mammary CID-9 cells Reproduction, March 1, 2004; 127(3): 397 - 406. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. D'Acquisto, M. J. May, and S. Ghosh Inhibition of Nuclear Factor Kappa B (NF-B):: An Emerging Theme in Anti-Inflammatory Therapies Mol. Interv., February 1, 2002; 2(1): 22 - 35. [Abstract] [Full Text] [PDF]
|
|