Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis

Mengozzi, Manuela, Cervellini, Ilaria, Bigini, Paolo, Martone, Sara, Biondi, Antonella, Pedotti, Rosetta, Gallo, Barbara, Barbera, Sara, Mennini, Tiziana, Boraso, Mariaserena, Marinovich, Marina, Petit, Edwige, Bernaudin, Myriam, Bianchi, Roberto, Viviani, Barbara and Ghezzi, Pietro (2008) Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis. Molecular Medicine, 14 (11-12). pp. 682-688. ISSN 1076-1551

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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)-1 alpha, but not HIF-2 alpha, 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)-gamma and tumor necrosis factor (TNF), and these cytokines inhibited EPO production in vitro in both neuronal and glial cells. 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.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Subjects: R Medicine > RB Pathology > RB151 Theories of disease. Etiology. Pathogenesis
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Depositing User: Manuela Mengozzi
Date Deposited: 19 Aug 2011 11:26
Last Modified: 17 Jun 2013 08:33
URI: http://sro.sussex.ac.uk/id/eprint/7201
Google Scholar:7 Citations
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