title: Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis.
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.
authors.affiliation: Mario Negri Institute for Pharmacological Research, Milan, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Mengozzi
authors.forename: Ilaria
authors.initials: I
authors.lastname: Cervellini
authors.forename: Paolo
authors.initials: P
authors.lastname: Bigini
authors.forename: Sara
authors.initials: S
authors.lastname: Martone
authors.forename: Antonella
authors.initials: A
authors.lastname: Biondi
authors.forename: Rosetta
authors.initials: R
authors.lastname: Pedotti
authors.forename: Barbara
authors.initials: B
authors.lastname: Gallo
authors.forename: Sara
authors.initials: S
authors.lastname: Barbera
authors.forename: Tiziana
authors.initials: T
authors.lastname: Mennini
authors.forename: Mariaserena
authors.initials: M
authors.lastname: Boraso
authors.forename: Marina
authors.initials: M
authors.lastname: Marinovich
authors.forename: Edwige
authors.initials: E
authors.lastname: Petit
authors.forename: Myriam
authors.initials: M
authors.lastname: Bernaudin
authors.forename: Roberto
authors.initials: R
authors.lastname: Bianchi
authors.forename: Barbara
authors.initials: B
authors.lastname: Viviani
authors.forename: Pietro
authors.initials: P
authors.lastname: Ghezzi
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016207:Cytokines / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism*; D004921:Erythropoietin / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000494:pharmacology; D051379:Mice; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016207:Cytokines; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014409:Tumor Necrosis Factor-alpha; D004921:Erythropoietin; D007371:Interferon-gamma