Blockage of the macrophage migration inhibitory factor expression by short interference RNA inhibited the rejection of an allogeneic tracheal graft.

Abstract

We investigated the inhibitory effect of blocking the macrophage migration inhibitory factor (MIF) on the fibrous obstruction of a transplanted allograft in a murine model of obstructive bronchiolitis (OB). Tracheal grafts from C57BL/6 mice were transplanted into a subcutaneous pouch of BALB/c. Three days after transplantation, liposome including short interference (si) RNA for MIF was injected into the lumen of the grafts. The allografts were then harvested 7, 14 or 28 days after transplantation for an evaluation of the morphological changes. The MIF expression, which was ubiquitously recognized in the epithelium of allografts, decreased after the in vivo transfection of MIF siRNA. OB formation was therefore inhibited significantly more by the treatment with MIF siRNA than the allografts injected with empty liposome on the 14th day, however, no difference was observed between them on the 28th day. Treatment with MIF siRNA inhibits the destruction of tracheal allografts and OB formation in the early phase, and MIF was thus found to be one of the major cytokines involved in the rejection of the allogeneic trachea.