Institut National de la Santé et de la Recherche Médicale, U1016, Institut Cochin, Faculté de Médecine Cochin Port Royal, Paris, France.
PLoS One. 2013 Apr 23;8(4):e61050. doi: 10.1371/journal.pone.0061050. Print 2013.
The anemia of chronic disease (also called anemia of inflammation) is an acquired disorder of iron homeostasis associated with infection, malignancy, organ failure, trauma, or other causes of inflammation. It is now widely accepted that induction of hepcidin expression in response to inflammation might explain the characteristic hypoferremia associated with this condition. To determine the role of hepcidin in acute inflammation and the regulation of its receptor, the iron exporter, ferroportin, wild-type, heterozygote and hepcidin knockout mice (Hepc-/-) were challenged with sublethal doses of lipopolysaccharide (LPS). Six hours after injection, ferroportin mRNA and protein levels were assessed in the duodenum and the spleen and plasma iron was determined. Our results demonstrate that hepcidin is crucial, though not the sole mediator of LPS-mediated acute hypoferremia, and also that hepcidin major contribution relies on decreased ferroportin protein levels found in the spleen. Furthermore, we establish that LPS-mediated repression of the membrane iron transporter DMT1 and oxidoreductase Dcytb in the duodenum is independent of hepcidin. Finally, our results in the hepc+/- mice indicate that elevated hepcidin gene expression is not a prerequisite for the setting of hypoferremia during early inflammatory response, and they highlight the intimate crosstalk between inflammatory and iron-responsive pathways for the control of hepcidin.
慢性病贫血（也称为炎症性贫血）是一种后天铁稳态紊乱，与感染、恶性肿瘤、器官衰竭、创伤或其他炎症原因有关。现在人们普遍认为，铁调素表达的诱导是对炎症的反应，可能解释了这种情况下特征性的低铁血症。为了确定铁调素在急性炎症中的作用及其受体（铁输出蛋白， ferroportin）的调节作用，野生型、杂合型和铁调素敲除小鼠（Hepc-/-）用亚致死剂量的脂多糖（LPS）进行了挑战。注射后 6 小时，评估了十二指肠和脾脏中的 ferroportin mRNA 和蛋白水平，并测定了血浆铁。我们的结果表明，铁调素虽然不是 LPS 介导的急性低铁血症的唯一介质，但却是至关重要的，而且铁调素的主要作用依赖于脾脏中发现的 ferroportin 蛋白水平降低。此外，我们确定 LPS 介导的十二指肠中膜铁转运蛋白 DMT1 和氧化还原酶 Dcytb 的抑制作用与铁调素无关。最后，我们在 Hepc+/- 小鼠中的结果表明，铁调素基因表达的升高不是早期炎症反应期间低铁血症发生的先决条件，并且强调了炎症和铁反应途径之间的密切相互作用，以控制铁调素。
