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Molecular Medicine

, Volume 14, Issue 11–12, pp 682–688 | Cite as

Endogenous Erythropoietin as Part of the Cytokine Network in the Pathogenesis of Experimental Autoimmune Encephalomyelitis

  • Manuela Mengozzi
  • Ilaria Cervellini
  • Paolo Bigini
  • Sara Martone
  • Antonella Biondi
  • Rosetta Pedotti
  • Barbara Gallo
  • Sara Barbera
  • Tiziana Mennini
  • Mariaserena Boraso
  • Marina Marinovich
  • Edwige Petit
  • Myriam Bernaudin
  • Roberto Bianchi
  • Barbara Viviani
  • Pietro Ghezzi
Research Article

Abstract

Erythropoietin (EPO) is of great interest as a therapy for many of the central nervous system (CNS) diseases and its administration is protective in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis (MS). Endogenous EPO is induced by hypoxic/ischemic injury, but little is known about its expression in other CNS diseases. We report here that EPO expression in the spinal cord is induced in mouse models of chronic or relapsing-remitting EAE, and is prominently localized to motoneurons. We found a parallel increase of hypoxia-inducible transcription factor (HIF)-1α, but not HIF-2α, at the mRNA level, suggesting a possible role of non-hypoxic factors in EPO induction. EPO mRNA in the spinal cord was co-expressed with interferon (IFN)-γ and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glialcells. Given the known inhibitory effect of EPO on neuroinflammation, our study indicates that EPO should be viewed as part of the inflammatory/anti-inflammatory network in MS.

Notes

Acknowledgments

This study was supported in part by the Kenneth S Warren Institute, Ossining, NY, the Fondazione CARIPLO, Milan, Italy (to PG), the French Centre National de la Recherche Scientifique (CNRS) and the French Ministère de L’Enseignement Supérieur et de la Recherche (to EP and M Bernaudin).

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Copyright information

© Feinstein Institute for Medical Research 2008

Authors and Affiliations

  • Manuela Mengozzi
    • 1
  • Ilaria Cervellini
    • 1
  • Paolo Bigini
    • 1
  • Sara Martone
    • 1
  • Antonella Biondi
    • 1
  • Rosetta Pedotti
    • 2
  • Barbara Gallo
    • 2
  • Sara Barbera
    • 1
  • Tiziana Mennini
    • 1
  • Mariaserena Boraso
    • 3
  • Marina Marinovich
    • 3
  • Edwige Petit
    • 4
  • Myriam Bernaudin
    • 4
  • Roberto Bianchi
    • 1
  • Barbara Viviani
    • 3
  • Pietro Ghezzi
    • 1
  1. 1.Mario Negri Institute for Pharmacological ResearchMilanoItaly
  2. 2.Immunology and Muscular Pathology UnitNeurological Institute Foundation Carlo BestaMilanItaly
  3. 3.Department of Pharmacological SciencesUniversity of MilanMilanItaly
  4. 4.Centre d’Imagerie-Neurosciences et Applications aux Pathologies (CI-NAPS), UMR 6232Université de Caen Basse-Normandie, Université Paris Descartes, CNRS, CEA; CERVOxy group “Hypoxia and Cerebrovascular Pathophysiology,” Centre CyceronCaenFrance

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