Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria.
Interleukin-10 regulates hepcidin in Plasmodium falciparum malaria.
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DOI：
10.1371/journal.pone.0088408
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Casals-Pascual C
中科院分区：
文献类型：
--
作者：
Huang H;Lamikanra AA;Alkaitis MS;Thézénas ML;Ramaprasad A;Moussa E;Roberts DJ;Casals-Pascual C
急性疟疾性贫血仍然是一个主要的公共卫生问题。Hepcidin是控制铁可用性的主要激素，在急性和无症状寄生虫病期间升高。了解感染期间hepcidin升高和铁可得性降低的作用和机制，对于建立以证据为基础的疟疾性贫血管理指南至关重要。我们最近的临床证据表明IL-10在急性恶性疟原虫疟疾患者中调控hepcidin的潜在作用。我们测定了原代巨噬细胞和肝癌细胞系HepG2在IL-10、IL-6和恶性疟原虫感染红细胞刺激下的hepcidin分泌情况。我们观察到，当这些细胞与恶性疟原虫感染的红细胞共培养时，原代巨噬细胞中IL-10和IL-6的产生增加。我们发现IL-10诱导原代巨噬细胞分泌hepcidin呈剂量依赖性，但在HepG2细胞中没有。这些作用是通过信号转导和转录激活因子（STAT） 3磷酸化介导的，并被特定的STAT3抑制剂完全消除。IL-10可在原代巨噬细胞中直接调节hepcidin，而在HepG2细胞中不起调节作用。这种效应可由恶性疟原虫调节。结果与IL-10在感染急性期调节铁代谢的作用一致。
Acute malarial anemia remains a major public health problem. Hepcidin, the major hormone controlling the availability of iron, is raised during acute and asymptomatic parasitemia. Understanding the role and mechanism of raised hepcidin and so reduced iron availability during infection is critical to establish evidence-based guidelines for management of malaria anemia. Our recent clinical evidence suggests a potential role of IL-10 in the regulation of hepcidin in patients with acute P. falciparum malaria. We have measured secretion of hepcidin by primary macrophages and the hepatoma cell line HepG2 stimulated with IL-10, IL-6 and Plasmodium falciparum-infected erythrocytes. We have observed that IL-10 and IL-6 production increased in primary macrophages when these cells were co-cultured with Plasmodium falciparum–infected erythrocytes. We found that IL-10 induced hepcidin secretion in primary macrophages in a dose-dependent manner but not in HepG2 cells. These effects were mediated through signal transducer and activator of transcription (STAT) 3-phosphorylation and completely abrogated by a specific STAT3 inhibitor. IL-10 can directly regulate hepcidin in primary macrophages but not in HepG2 cells. This effect can be modulated by Plasmodium falciparum. The results are consistent with a role for IL-10 in modulating iron metabolism during acute phase of infection.
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影响因子：
4.4
作者：
Tilg, H;Ulmer, H;Weiss, G
通讯作者：
Weiss, G
影响因子：
82.9
作者：
通讯作者：
--
影响因子：
64.8
作者：
Roberts, D J;Craig, A G;Berendt, A R;Pinches, R;Nash, G;Marsh, K;Newbold, C I
通讯作者：
Newbold, C I
DOI：
10.3324/haematol.2012.065854
发表时间：
2012-11-01
期刊：
HAEMATOLOGICA-THE HEMATOLOGY JOURNAL
影响因子：
--
作者：
Casals-Pascual, Climent;Huang, Honglei;Roberts, David J.
通讯作者：
Roberts, David J.
影响因子：
20.3
作者：
Armitage, Andrew E.;Eddowes, Lucy A.;Drakesmith, Hal
通讯作者：
Drakesmith, Hal