研究动态
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炎症在小鼠的骨骼和脾脏中改变铁分布。

Inflammation alters iron distribution in bone and spleen in mice.

发表日期:2023 Sep 20
作者: JuOae Chang, Melis Debreli Coskun, Jonghan Kim
来源: Bone & Joint Journal

摘要:

炎症相关性贫血降低了患有各种炎症性疾病(如感染、自身免疫性疾病和癌症)的数十亿患者的生活质量,这些疾病与持续的免疫激活状态相关。虽然适当利用铁,一种对红细胞生成至关重要的养分金属,对预防贫血非常重要,但在炎症状态下,机体铁的稳态调节的改变尚未完全理解。因此,我们试图研究小鼠炎症期间铁和与铁相关分子的分布的时间和空间变化。为了诱导炎症,我们将C57BL/6J小鼠每周注射松节油3周,导致贫血,脾脏、十二指肠和肝脏中铁运载蛋白,即细胞铁输出蛋白,的蛋白表达降低,十二指肠和脾脏中铁储存增加。通过口服59Fe后的示踪动力学研究发现,与注射生理盐水小鼠相比,注射松节油的小鼠脾脏中的铁更多,而股骨中的铁更少,表明炎症期间铁的分布存在组织特异性异常。然而,在松节油注射后,铁的利用于红细胞产生没有差异;相反,血清血红蛋白抑素水平和乳酸脱氢酶活性增加,表明炎症导致红细胞破坏增加。我们的发现提供了对炎症期间铁的分布和利用的时间和空间变化的改进理解。The Author(s) 2023. Published by Oxford University Press.
Anemia of inflammation (or inflammation-associated anemia) decreases the quality of life in billions of patients suffering from various inflammatory diseases, such as infection, autoimmune diseases, and cancer, associated with a prolonged state of immune activation. While proper utilization of iron, a nutrient metal essential for erythropoiesis, is important for the prevention of anemia, the alteration of body iron homeostasis upon inflammation, which can contribute to the development of anemia, is not completely understood. Thus, we sought to examine temporal and spatial changes in the distribution of iron and iron-associated molecules during inflammation in mice. To induce inflammation, C57BL/6 J mice were injected with turpentine oil weekly for 3 weeks, which resulted in anemia, decreased protein expression of ferroportin, a cellular iron exporter, in the spleen, duodenum, and liver, and increased iron stores in the duodenum and spleen. Tracer kinetic studies after oral administration of 59Fe revealed that more iron was found in the spleen and less in the femur bone in turpentine oil-injected mice compared to the saline-injected mice, indicating tissue-specific abnormalities in iron distribution during inflammation. However, there was no difference in the utilization of iron for red blood cell production after turpentine oil injection; instead, serum hemopexin level and lactate dehydrogenase activity were increased, suggesting increased red blood cell destruction upon inflammation. Our findings provide an improved understanding of temporal and spatial changes in the distribution and utilization of iron during inflammation.The Author(s) 2023. Published by Oxford University Press.