Marques F, Falcao A M, Sousa J C, Coppola G, Geschwind D, Sousa N, Correia-Neves M, Palha J A
Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Braga, Portugal.
Endocrinology. 2009 Jun;150(6):2822-8. doi: 10.1210/en.2008-1610. Epub 2009 Feb 12.
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.
铁对于正常细胞内稳态至关重要，但过量的铁会促进自由基形成，从而产生有害影响。因此，铁代谢受到严格调控。在此，我们表明，调节全身铁代谢的机制可能也控制着铁在血 - 脉络丛 - 脑脊液（CSF）屏障处释放到脑内的过程。给小鼠腹腔注射脂多糖（LPS）会引发脉络丛中编码铁调素（铁稳态的关键调节因子）的基因的短暂转录，这与脑脊液中前铁调素检测量的增加相关。同样，几种其他与铁相关的基因的表达在脉络丛中也受到炎症刺激的影响。利用大鼠脉络丛上皮细胞的原代培养，我们表明这种反应不仅由LPS直接触发，还由炎症反应时血液中表达增加的分子（如IL - 6）触发。这些信号分子的细胞内传导因子包括磷酸化的信号转导和转录激活因子3以及LPS给药后不久其mRNA水平就升高的SMAD家族成员4。脉络丛 - 脑脊液屏障在调节铁代谢中的这一新作用可能在限制微生物生长所需的铁供应方面特别重要，并且在已报道存在炎症潜在成分的神经退行性疾病中也具有重要意义。
