MISC

2007年2月

A novel DNA vaccine targeting macrophage migration inhibitory factor protects joints from inflammation and destruction in murine models of arthritis

ARTHRITIS AND RHEUMATISM
  • Shin Onodera
  • ,
  • Shigeki Ohshima
  • ,
  • Harukazu Tohyama
  • ,
  • Kazunori Yasuda
  • ,
  • Jun Nishihira
  • ,
  • Yoichiro Iwakura
  • ,
  • Ikkei Matsuda
  • ,
  • Akio Minami
  • ,
  • Yoshikazu Koyama

56
2
開始ページ
521
終了ページ
530
記述言語
英語
掲載種別
DOI
10.1002/art.22407
出版者・発行元
WILEY-LISS

Objective. Previous studies have demonstrated that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibodies decreases joint inflammation and destruction in a type 11 collagen-induced arthritis model in mice. The aim of this study was to develop and describe a simple and effective method of active immunization that induces anti-MIF autoantibodies, which may neutralize MIF bioactivity.
Methods. We developed a MIF DNA vaccine by introducing oligonucleotides encoding a tetanus toxoid (TTX) Th cell epitope into the complementary DNA sequence of murine MIF. Mice were injected with this construct in conjunction with electroporation. The ability of this immunization to inhibit the development of collagen antibody-induced arthritis (CAIA) in BALB/c mice and spontaneous autoimmune arthritis in interleukin-1 receptor antagonist (IL-IRa)-deficient mice was then evaluated.
Results. Mice that received the MIF/TTX DNA vaccine developed high titers of autoantibodies that reacted to native MIF. Compared with unvaccinated mice, vaccinated mice also produced less serum tumor necrosis factor a after receiving an intravenous injection of lipopolysaccharide. In addition, vaccination with MIF/TTX DNA resulted in significant amelioration of both CAIA in BALB/c mice and symptoms of autoimmune arthritis in IL-1Ra-knockout mice.
Conclusion. These results suggest that MIF/TTX DNA vaccination may be useful for ameliorating the symptoms of rheumatoid arthritis.

Web of Science ® 被引用回数 : 29

リンク情報
DOI
https://doi.org/10.1002/art.22407
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000244145300016&DestApp=WOS_CPL

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