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

Abstract

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.

Macrophage Migration Inhibitory Factor Is Upregulated in an Endotoxin-Induced Model of Bladder Inflammation in Rats

“…We have localized MIF to neurons in the MPG, sympathetic chain, L6-S1 DRG, and lumbosacral spinal cord of the rat, (8) and MIF expression in the brain, spinal cord, and peripheral nerves of the rat has been reported by others. (38,39) Intravesical LPS increased MIF protein and mRNA in the lumbosacral spinal cord and the DRG, similar to our earlier findings using The resulting PCR products were resolved on 2% agarose gels and used to determine a relative intensity ratio. Data are expressed as mean gene expression ratio (area-intensity of gene-specific band divided by area-intensity of 18S rRNA band).…”

Macrophage migration inhibitory factor activates inflammatory responses of astrocytes through interaction with CD74 receptor

“…MIF has been found ubiquitously expressed in the different cell types of CNS and PNS, such as neuron, microglia and glial cells [15, 33, 34]. The cytokine has been released to carry out function through paracrine and autocrine action [23, 35].…”

Contribution of Macrophage Migration Inhibitory Factor to Extracellular Signal-regulated Kinase Activation by Oxidative Stress in Cardiomyocytes

“…Rat recombinant MIF was expressed in Escherichia coli and purified to homogeneity as described previously (24). A polyclonal anti-rat MIF antibody was generated by immunizing New Zealand White rabbits with recombinant rat MIF as reported previously (25).…”