• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Hepcidin as the central mediator of anemia of inflammation.
【24h】

Hepcidin as the central mediator of anemia of inflammation.

机译：铁调素是炎症性贫血的主要介质。

获取原文
获取原文并翻译 | 示例
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Anemia of inflammation (AI, anemia of chronic disease) occurs during a wide variety of inflammatory disorders including infections, autoimmune diseases, renal failure, and malignancy. It is associated with significant morbidity, may increase mortality rates in some diseases, and increases healthcare costs dramatically. The principal finding that differentiates AI from other chronic anemias is hypoferremia in the setting of preserved iron stores. Until recently, little was known about the normal molecular regulation of iron transport or its dysregulation in AI. The discovery of the negative iron-regulatory hormone hepcidin and the cellular iron exporter ferroportin in the past 7 years strongly suggested that hepcidin may be the mediator of AI. This work shows that the effect of increased hepcidin levels recapitulates the findings of AI. We show that mice given exogenous hepcidin rapidly develop hypoferremia in a dose-dependent fashion. Hepcidin traffics to organs rich in ferroportin supporting the in vitro finding that hepcidin induces the degradation of ferroportin. Furthermore, mice with tumors overexpressing hepcidin develop more severe hypoferremia and anemia than mice with control tumors. This work also demonstrates that hepcidin is directly regulated by inflammatory mediators. We found that IL-6 is an important regulator of hepcidin, especially during acute inflammation, but that other mediators may play a role during prolonged inflammation. Finally we demonstrate that there is a feedback mechanism to limit the severity of anemia that occurs in response to increased hepcidin. Hepcidin is decreased during phlebotomy-induced anemia but inhibitors of erythropoiesis reverse the effect of anemia. These results indicate that the suppression of hepcidin during anemia is predominantly through increased erythropoiesis or the fall in serum or tissue iron secondary to increased iron utilization. In the aggregate, the studies presented in this thesis show that hepcidin is the principal mediator of the anemia of inflammation.
机译：炎症性贫血（AI，慢性疾病性贫血）发生在各种炎症性疾病中，包括感染，自身免疫性疾病，肾衰竭和恶性肿瘤。它与高发病率有关，可能会增加某些疾病的死亡率，并显着增加医疗费用。将AI与其他慢性贫血区分开来的主要发现是在保存铁的过程中发生了低铁血症。直到最近，人们对AI中铁转运的正常分子调控或其失调知之甚少。过去7年中发现的负铁调节激素铁调素和细胞铁输出铁转运蛋白铁转运蛋白强烈表明，铁调素可能是AI的介体。这项工作表明，铁调素水平增加的影响概括了AI的发现。我们显示给小鼠外源铁调素以剂量依赖性方式迅速发展低铁血症。铁调素运输到富含铁转运蛋白的器官，这支持了体外研究发现铁调素诱导铁转运蛋白的降解。此外，具有过度表达铁调素的肿瘤的小鼠比具有对照肿瘤的小鼠发生更严重的低铁血症和贫血。这项工作还证明了铁调素是由炎症介质直接调节的。我们发现IL-6是铁调素的重要调节剂，尤其是在急性炎症过程中，但其他介质可能在长时间炎症中起作用。最后，我们证明了有一种反馈机制可以限制因铁调素增加而引起的贫血的严重程度。 Hepcidin在静脉切开术引起的贫血过程中减少，但促红细胞生成素的抑制剂逆转了贫血的作用。这些结果表明，贫血过程中铁调素的抑制主要是通过增加红细胞生成或由于铁利用增加引起的血清或组织铁含量下降。总体而言，本论文提出的研究表明，铁调素是炎症性贫血的主要介质。

著录项

  • 作者

    Rivera, Seth.;

  • 作者单位

    University of California, Los Angeles.;

  • 授予单位 University of California, Los Angeles.;
  • 学科 Pathology.;Immunology.
  • 学位 Ph.D.
  • 年度 2006
  • 页码 120 p.
  • 总页数 120
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号