Molecular function of macrophage migration inhibitory factor and a novel therapy for inflammatory bowel disease.
Macrophage migration inhibitory factor (MIF) is a unique protein that participates in inflammation, immune responses, and cell growth. An array of in vitro and in vivo experiments has demonstrated that MIF is profoundly involved in the pathogenesis of acute and chronic inflammatory disorders, such as inflammatory bowel disease (IBD). Blockade of MIF bioactivities by either neutralizing anti-MIF antibodies or antagonists prevents inflammatory cytokine cascade, which strongly suggests that an anti-MIF therapeutic strategy is feasible for treatment of IBD. Recently, we developed a new therapeutic approach for IBD by administration of antisense MIF oligonucleotides in conjugation with schizophyllan (SPG), a member of the glucan family. SPG specifically binds Dectin-1 expressed in antigen-presenting cells (APCs), and the antisense MIF/SPG complex is incorporated into the cells. In in vivo experiments of colitis models in mice, we found that intraperitoneal administration of the complex ameliorated the clinical signs of colitis and improved the histological scores. This novel therapy designed to knock down the MIF production in APCs is expected to be clinically applicable for the treatment of IBD.
Department of Medical Management and Informatics, Hokkaido Information University, Ebetsu, Hokkaido, Japan. nishihira@do-johodai.ac.jp
Jun
J
Nishihira
D000818:Animals; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems; D055785:Gene Knockdown Techniques; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D012566:Sizofiran / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D000099181:Dectin-1
D007155:Immunologic Factors; D019746:Intramolecular Oxidoreductases; D037181:Lectins, C-Type; D008263:Macrophage Migration-Inhibitory Factors; D016376:Oligonucleotides, Antisense; D012566:Sizofiran; C546929:CLEC7A protein, human; D000099181:Dectin-1; C515598:MIF protein, human