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|Título:||Altered iron metabolism is part of the choroid plexus response to peripheral inflammation.|
Falcão, Ana M.
Sousa, João Carlos
Geschwind, Daniel H.
Neves, Margarida Correia
Palha, Joana Almeida
|Resumo(s):||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.|
|Versão da editora:||http://endo.endojournals.org/content/150/6/2822.full.pdf+html|
|Aparece nas coleções:||ICVS - Artigos em Revistas Internacionais com Referee|
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|marques f_ endocrinology 2009.pdf||1,46 MB||Adobe PDF||Ver/Abrir|