DNA vaccination targeting macrophage migration inhibitory factor prevents murine experimental colitis.
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.
Hokkaido Information University, and Department of Gastroenterology and Hematology, Hokkaido University Graduate School of Medicine, Sapporo, Japan. tatsuya-ohkawara@umin.ac.jp
T
T
Ohkawara
Y
Y
Koyama
S
S
Onodera
H
H
Takeda
M
M
Kato
M
M
Asaka
J
J
Nishihira
D000818:Animals; D000943:Antigens, Differentiation / Q000032:analysis / Q000276:immunology; D001323:Autoantibodies / Q000097:blood / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000517:prevention & control*; D016207:Cytokines / Q000032:analysis; D016264:Dextran Sulfate / Q000494:pharmacology; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009195:Peroxidase / Q000032:analysis; D019444:Vaccines, DNA / Q000627:therapeutic use*
D000943:Antigens, Differentiation; D001323:Autoantibodies; D016207:Cytokines; D008263:Macrophage Migration-Inhibitory Factors; D019444:Vaccines, DNA; C036763:monocyte-macrophage differentiation antigen; D016264:Dextran Sulfate; D009195:Peroxidase