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Up-regulation of macrophage migration-inhibitory factor expression after compression-induced spinal cord injury in rats

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Abstract

Macrophage migration inhibitory factor (MIF) is a multipotential protein that acts as a pro-inflammatory cytokine, pituitary hormone, immunoregulator, and mitogen. To elucidate function of MIF in spinal cord injury, we examined expression of MIF after compression-induced spinal cord injury using Northern blot analysis, in situ hybridization and immunohistochemistry. The MIF mRNA was up-regulated in injured spinal cord, peaking 3 days after injury shown by Northern blot analysis. In situ hybridization revealed up-regulation of MIF in microglia accumulating in the lesion epicenter 3 days after injury and astrocytes around the cystic cavity 1 week after injury. Double staining showed co-localization of MIF and tomato lectin in the lesioned site, indicating that microglia accumulating to the lesion epicenter express MIF. The time course of MIF expression is different from that of previous reports about cytokine expression peaking at earlier time points; thus, it is unlikely that MIF acts as a pro-inflammatory factor in the present study. The MIF may contribute to proliferation of astrocytes around the lesioned site in spinal cord injury because of its cell proliferation-promoting property.

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References

  1. Abe R, Shimizu T, Ohkawara A, and Nishihira J (2000) Enhancement of macrophage migration inhibitory factor (MIF) expression in injured epidermis and cultured fibroblasts. Biochim Biophys Acta 1500:1–9

    CAS  PubMed  Google Scholar 

  2. Bernhagen J, Calandra T, Mitchell RA, Martin SB, Tracy KJ, Voelter W, Manogue KR, Cerami A, Bucala R (1993) MIF is a pituitary-derived cytokine that potentiates lethal endotoxaemia. Nature 365:756–759

    CAS  PubMed  Google Scholar 

  3. Bloom BR, Bennet B (1966) Mechanism of a reaction in vitro associated with delayed-type hypersensitivity. Science 153:80–82

    CAS  PubMed  Google Scholar 

  4. Bucala R (1996) MIF re-discovered: pituitary hormone and glucocorticoid-induced regulator of cytokine production. FASEB J 7:19–24

    Article  CAS  Google Scholar 

  5. Calandra T, Bucala R (1995) Macrophage migration inhibitory factor: a counter-regulator of glucocorticoid action and critical mediator of septic shock. J Inflamm 47:39–51

    CAS  PubMed  Google Scholar 

  6. Torre JC de la (1981) Spinal cord injury. Review of basic and applied research. Spine 6:315–332

    PubMed  Google Scholar 

  7. Fujimoto S (1997) Identification of macrophage migration inhibitory factor (MIF) in rat spinal cord and its kinetics on experimental spinal cord injury. Hokkaido Med J 72:409–430 [in Japanese]

    CAS  Google Scholar 

  8. Hayashi M, Ueyama T, Nemoto K, Tamaki T, Semba E (2000) Sequential mRNA expression for immediate early genes, cytokines, and neurotrophins in spinal cord injury. J Neurotrauma 17:203–218

    CAS  PubMed  Google Scholar 

  9. Hashimoto M, Koda M, Ino H, Murakami M, Yamazaki M, Moriya H (2003) Upregulation of osteopontin expression in rat spinal cord microglia after traumatic injury. J Neurotrauma 20:287–296

    Article  PubMed  Google Scholar 

  10. Ikeda O, Murakami M, Ino H, Yamazaki M, Nemoto T, Koda M, Nakayama C, Moriya H (2001) Acute up-regulation of BDNF expression resulting from experimentally-induced injury in the rat spinal cord. Acta Neuropathol (Berl) 102:239–245

    Google Scholar 

  11. Ikeda O, Murakami M, Ino H, Yamazaki M, Koda M, Nakayama C, Moriya H (2002) Effects of brain-derived neurotrophic factor (BDNF) on compression-induced spinal cord injury: BDNF attenuates down-regulation of superoxide dismutase expression and promotes up-regulation of myelin basic protein expression. J Neuropathol Exp Neurol 61:142–153

    Google Scholar 

  12. Koda M, Murakami M, Ino H, Yoshinaga K, Ikeda O, Hashimoto M, Yamazaki M, Nakayama C, Moriya H (2002) Brain-derived neurotrophic factor suppresses delayed apoptosis of oligodendrocytes after spinal cord injury in rats. J Neurotrauma 19:777–785

    Article  PubMed  Google Scholar 

  13. Mitchell RA, Metz CN, Peng T, Bucala R (1999) Sustained mitogen-activated protein kinase (MAPK) and cytoplasmic phospholipase A2 activation by macrophage migration inhibitory factor (MIF). Regulatory role in cell proliferation and glucocorticoid action. J Biol Chem 274:18100–18106

    CAS  PubMed  Google Scholar 

  14. Nakamura M, Houghtling RA, MacArthur L, Bayer BM, Bregman BS (2003) Differences in cytokine gene expression profile between acute and secondary injury in adult rat spinal cord. Exp Neurol 184:313–325

    Article  CAS  PubMed  Google Scholar 

  15. Niino M, Ogata A, Kikuchi S, Tashiro K, Nishihira J (2000) Macrophage migration inhibitory factor in the cerebrospinal fluid of patients with conventional and optic-spinal forms of multiple sclerosis and neuro-Beçhet’s disease. J Neurol Sci 179:127–131

    Article  CAS  PubMed  Google Scholar 

  16. Nishibori M, Nakaya N, Tahara A, Kawabata M, Mori S, Saeki K (1996) Presence of macrophage migration inhibitory factor (MIF) in ependyma, astrocytes and neurons in the bovine brain. Neurosci Lett 213:193–196

    CAS  PubMed  Google Scholar 

  17. Nishino T, Bernhagen J, Shiiki H, Calandra T, Dohi K, Bucala R (1995) Localization of macrophage migration inhibitory factor (MIF) to secretory granules within the corticotrophic and thyrotrophic cells of the pituitary gland. Mol Med 1:781–788

    CAS  PubMed  Google Scholar 

  18. Nishio Y, Nishihira J, Ishibashi T, Kato H, Minami A (2002) Role of macrophage migration inhibitory factor (MIF) in peripheral nerve regeneration: anti-MIF antibody induces delay of nerve regeneration and the apoptosis of Schwann cells. Mol Med 8:509–520

    CAS  PubMed  Google Scholar 

  19. Ogata A, Nishihira J, Suzuki T, Nagashima K, Tashiro K (1998) Identification of macrophage migration inhibitory factor mRNA expression in neural cells of the rat brain by in situ hybridization. Neurosci Lett 246:173–177

    Article  CAS  PubMed  Google Scholar 

  20. Onodera S, Nishihira J, Iwabuchi K, Koyama Y, Tanaka S, Yoshida K, Minami A (2002) Macrophage migration inhibitory factor up-regulates MMP-9 amd -13 in rat osteoblasts. Relevance to intracellular signaling pathways. J Biol Chem 277:7865–7874

    Article  CAS  PubMed  Google Scholar 

  21. Schwab ME, Bartholdi D (1996) Degeneration and regeneration of axons in the lesioned spinal cord. Physiol Rev 76:319–370

    CAS  PubMed  Google Scholar 

  22. Tator CH, Fehlings MG (1991) Review of the secondary injury theory of acute spinal cord trauma with emphasis on vascular mechanisms. J Neurosurg 75:15–26

    CAS  PubMed  Google Scholar 

  23. Wang XK, Louden C, Yue TL, Ellison JA, Barone FC, Solleveld HA, Feuerstein GZ (1998) Delayed expression of osteopontin after focal stroke in the rat. J Neurosci 18:2075–2083

    CAS  PubMed  Google Scholar 

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Acknowledgement

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.

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Correspondence to Masao Koda.

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Koda, M., Nishio, Y., Hashimoto, M. et al. Up-regulation of macrophage migration-inhibitory factor expression after compression-induced spinal cord injury in rats. Acta Neuropathol 108, 31–36 (2004). https://doi.org/10.1007/s00401-004-0853-z

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  • DOI: https://doi.org/10.1007/s00401-004-0853-z

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