Document Detail


Endogenous erythropoietin as part of the cytokine network in the pathogenesis of experimental autoimmune encephalomyelitis.
MedLine Citation:
PMID:  18670620     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-07-30
Journal Detail:
Title:  Molecular medicine (Cambridge, Mass.)     Volume:  14     ISSN:  1528-3658     ISO Abbreviation:  Mol. Med.     Publication Date:    2008 Nov-Dec
Date Detail:
Created Date:  2008-11-14     Completed Date:  2009-05-12     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9501023     Medline TA:  Mol Med     Country:  United States    
Other Details:
Languages:  eng     Pagination:  682-8     Citation Subset:  IM    
Affiliation:
Mario Negri Institute for Pharmacological Research, Milan, Italy.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line, Tumor
Cytokines / metabolism*
Encephalomyelitis, Autoimmune, Experimental / metabolism*
Erythropoietin / genetics,  metabolism*,  physiology*
Female
Gene Expression / drug effects
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Immunohistochemistry
Interferon-gamma / pharmacology
Mice
Reverse Transcriptase Polymerase Chain Reaction
Spinal Cord / metabolism
Tumor Necrosis Factor-alpha / pharmacology
Chemical
Reg. No./Substance:
0/Cytokines; 0/Hif1a protein, mouse; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Tumor Necrosis Factor-alpha; 11096-26-7/Erythropoietin; 82115-62-6/Interferon-gamma
Comments/Corrections

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