Identification of macrophage migration inhibitory factor (MIF) in rat peripheral nerves: its possible involvement in nerve regeneration.

Macrophage migration inhibitory factor (MIF) is known as a pluripotent immunoregulatory cytokine involved in T-cell activation and inflammatory responses; however, no study on this protein in the peripheral nervous systems has been carried out. We here demonstrated for the first time expression of MIF mRNA and MIF protein in rat sciatic nerves by reverse transcription-polymerase chain reaction, Western blotting, and immunohistochemistry. Immunohistochemical analysis revealed positive staining of MIF, which was largely observed in Schwann cells. Furthermore, we examined MIF mRNA expression in the sciatic nerves by Northern blot analysis in the case of nerve transection. In both proximal and distal segments, the level of MIF mRNA started to increase 12 h after the nerve transection. The level remained high from 24 h up to day 7 after the injury. During the period from days 14 to 21, MIF mRNA sharply decreased to the pre-transection level. In immunohistochemistry, positive staining of MIF was largely observed in axons as well as non-neuronal cells in proximal segments at day 4 after transection. In the distal segments, contrastingly, endoneurial fibroblasts or Schwann cells migrating into neuronal fibers showed positive staining with Wallerian degeneration. Although the precise functions of MIF in the peripheral nerves remain to be elucidated, the present results could represent a major departure from the current state of knowledge, revealing a novel function in the degenerative-regenerative process.