DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis

Clin Exp Immunol. 2011 Jan;163(1):113-22. doi: 10.1111/j.1365-2249.2010.04277.x. Epub 2010 Nov 9.

Abstract

Previous studies have shown that neutralization of macrophage migration inhibitory factor (MIF) by anti-MIF antibody reduces intestinal inflammation in mice. In this study we tested whether or not anti-MIF autoantibody induced by DNA vaccine targeting MIF protects mice against experimental colitis. Mice were administered a MIF-deoxyribonucleic acid (DNA) vaccine by introducing oligonucleotides encoding helper T epitope into the cDNA sequence of murine MIF by in vivo electroporation. Preventive effects of this method against dextran sulphate sodium-induced (DSS) colitis were evaluated. Mice administered with MIF-DNA vaccine raised values of autoantibody significantly. The clinical and histological findings of colitis induced by 3·0% DSS solution were ameliorated significantly in mice treated with MIF-DNA vaccine compared with saline or pCAGGS-treated mice given DSS. Myeloperoxidase activity, infiltration of F4/80-positive staining cells and the levels of proinflammatory cytokines were suppressed in the colon of MIF-DNA vaccine treated mice compared with saline or pCAGGS-treated mice exposed to DSS. Our results suggest that immunization with helper T epitope DNA-vaccine targeting MIF may be a useful approach for the treatment of colitis including inflammatory bowel diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Differentiation / analysis
  • Antigens, Differentiation / immunology
  • Autoantibodies / blood
  • Autoantibodies / immunology
  • Colitis / chemically induced
  • Colitis / prevention & control*
  • Cytokines / analysis
  • Dextran Sulfate / pharmacology
  • Macrophage Migration-Inhibitory Factors / antagonists & inhibitors*
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Peroxidase / analysis
  • Vaccines, DNA / therapeutic use*

Substances

  • Antigens, Differentiation
  • Autoantibodies
  • Cytokines
  • Macrophage Migration-Inhibitory Factors
  • Vaccines, DNA
  • monocyte-macrophage differentiation antigen
  • Dextran Sulfate
  • Peroxidase