Journal
DRUG DESIGN DEVELOPMENT AND THERAPY
Volume 11, Issue -, Pages 2997-3007Publisher
DOVE MEDICAL PRESS LTD
DOI: 10.2147/DDDT.S145421
Keywords
NF-kappa B decoy oligodeoxynucleotides; collagen-induced arthritis; dendritic cells; rheumatoid arthritis
Categories
Funding
- National Natural Sciencse Foundation of China [81660361]
- Guiyang Technology Bureau [GY2015-38]
- Guizhou Medical University [GY2015-38]
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Dendritic cells (DCs) play an important role in the initiation of autoimmunity in rheumatoid arthritis (RA); therefore, the use of DCs needs to be explored to develop new therapeutic approaches for RA. Here, we investigated the therapeutic effect of bovine type II collagen (BIIC)-loaded DCs modified with NF-kappa B decoy oligodeoxynucleotides (ODNs) on collagen-induced arthritis (CIA) in rats and explored the underlying mechanisms. DCs treated with BIIC and NF-kappa B decoy ODNs exhibited features of immature DCs with low levels of costimulatory molecule (CD80 and CD86) expression. The development of arthritis in rats with CIA injected with BIIC + NF-kappa B decoy ODN-propagated DCs (BIIC-decoy DCs) was significantly ameliorated compared to that in rats injected with BIIC-propagated DCs or phosphate-buffered saline. We also found that the BIIC-decoy DCs exerted antiarthritis effects by inhibiting self-lymphocyte proliferative response and suppressing IFN-gamma and anti-BIIC antibody production and inducing IL-10 antibody production. Additionally, antihuman serum antibodies were successfully produced in the rats treated with BIIC-decoy DCs but not in those treated with NF-kappa B decoy ODN-propagated DCs; moreover, the BIIC-decoy DCs did not affect immune function in the normal rats. These findings suggested that NF-kappa B decoy ODN-modified DCs loaded with a specific antigen might offer a practical method for the treatment of human RA.
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