Altered iron metabolism is part of the choroid plexus response to peripheral inflammation.
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/1822/29710 |
Resumo: | Iron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported. |
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Altered iron metabolism is part of the choroid plexus response to peripheral inflammation.Science & TechnologyIron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported.This work was supported by Grant POCTI/SAU-NEU/56618/2004 from Fundacao para a Ciencia e Tecnologia (Portugal) and a grant from The Dana Foundation (USA). F. M. is the recipient of postdoctoral fellowship, and A. M. F. is the recipient of a Ph. D., fellowship from Fundacao para a Ciencia e Tecnologia (Portugal).Endocrine SocietyUniversidade do MinhoMarques, FernandaFalcão, Ana M.Sousa, João CarlosCoppola, GiovanniGeschwind, Daniel H.Sousa, NunoNeves, Margarida CorreiaPalha, Joana Almeida2009-062009-06-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/1822/29710eng0013-722710.1210/en.2008-161019213835http://endo.endojournals.org/content/150/6/2822.full.pdf+htmlinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-07-21T12:09:06Zoai:repositorium.sdum.uminho.pt:1822/29710Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T19:00:27.836434Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
title |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
spellingShingle |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. Marques, Fernanda Science & Technology |
title_short |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
title_full |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
title_fullStr |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
title_full_unstemmed |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
title_sort |
Altered iron metabolism is part of the choroid plexus response to peripheral inflammation. |
author |
Marques, Fernanda |
author_facet |
Marques, Fernanda Falcão, Ana M. Sousa, João Carlos Coppola, Giovanni Geschwind, Daniel H. Sousa, Nuno Neves, Margarida Correia Palha, Joana Almeida |
author_role |
author |
author2 |
Falcão, Ana M. Sousa, João Carlos Coppola, Giovanni Geschwind, Daniel H. Sousa, Nuno Neves, Margarida Correia Palha, Joana Almeida |
author2_role |
author author author author author author author |
dc.contributor.none.fl_str_mv |
Universidade do Minho |
dc.contributor.author.fl_str_mv |
Marques, Fernanda Falcão, Ana M. Sousa, João Carlos Coppola, Giovanni Geschwind, Daniel H. Sousa, Nuno Neves, Margarida Correia Palha, Joana Almeida |
dc.subject.por.fl_str_mv |
Science & Technology |
topic |
Science & Technology |
description |
Iron is essential for normal cellular homeostasis but in excess promotes free radical formation and is detrimental. Therefore, iron metabolism is tightly regulated. Here, we show that mechanisms regulating systemic iron metabolism may also control iron release into the brain at the blood-choroid plexus-cerebrospinal fluid (CSF) barrier. Intraperitoneal administration of lipopolysaccharide (LPS) in mice triggers a transient transcription of the gene encoding for hepcidin, a key regulator of iron homeostasis, in the choroid plexus, which correlated with increased detection of pro-hepcidin in the CSF. Similarly, the expression of several other iron-related genes is influenced in the choroid plexus by the inflammatory stimulus. Using primary cultures of rat choroid plexus epithelial cells, we show that this response is triggered not only directly by LPS but also by molecules whose expression increases in the blood in response to inflammation, such as IL-6. Intracellular conveyors of these signaling molecules include signal transducer and activator of transcription 3, which becomes phosphorylated, and SMAD family member 4, whose mRNA levels increase soon after LPS administration. This novel role for the choroid plexus-CSF barrier in regulating iron metabolism may be particularly relevant to restrict iron availability for microorganism growth, and in neurodegenerative diseases in which an inflammatory underlying component has been reported. |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-06 2009-06-01T00:00:00Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/1822/29710 |
url |
http://hdl.handle.net/1822/29710 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
0013-7227 10.1210/en.2008-1610 19213835 http://endo.endojournals.org/content/150/6/2822.full.pdf+html |
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info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
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application/pdf |
dc.publisher.none.fl_str_mv |
Endocrine Society |
publisher.none.fl_str_mv |
Endocrine Society |
dc.source.none.fl_str_mv |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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