ラット脊髄におけるMacrophage Migration Inhibitory Factor(MIF)の発現及び脊髄損傷後急性期のMIF動態

Background: Among spinal cord injuries, secondary injury is considered to be a "reversible" process and seems to be a key target for the treatment of spinal cord injury. Recently, macrophage migration inhibitory factor (MIF) has been reevaluated as being one of the most important cytokines which act during wound healing, proliferation and differentiation of cells. However, the expression of MIF in the spinal cord has not been investigated yet. Purpose: The purpose of this paper is to demonstrate the MIF expression in normal rat spinal cord and to evaluate the kinetics of MIF after spinal cord injury. Materials ＆ Methods: Female Wistar (280-320g) rats were studied. Spinal cord injury was made by the clip compression method at the level of C7/Th1 (56 g, For 1 min.). The expression of MIF was examined by immunohistochemistry and northern blot analysis. MIF content in the cerebrospinal fluid(CSF) was measured by enzyme-linked immunosorbent as say s (ELISA). Furthermore, to examine the MIF function on neuronal cell, cell proliferation assay (MTS assay) was carried out using PC 12, pheochromocytoma cell line, and LN444, glioblastoma cell line, in the presence of anti-MIF monoclonal anti body. Results: MIF stain was positive in normal rat spinal cord white matter. The expression of MIF decreased between 1 hour and 6 hours after injury. It was found to have re-appeared 24 hours after injury. The kinetics of MIF mRNA expression showed reverse-correlation with those of the MIF positive stain. MIF content in CSF was found to be elevated soon after injury. MTS assay suggested that MIF had some proliferative function on neuronal cells. Conclusion: MIF exists in the rat white matter. And it's immediately released into the CSF and then re-synthesized 24-hr after injury. MIF shows a cell Proliferative function on neuronal cells. These results suggest that MIF plays an important role for secondary spinal cord injury.