Bacterial Cell Wall Constituents Induce Hepcidin Expression in Macrophages Through MyD88 Signaling
Bacterial Cell Wall Constituents Induce Hepcidin Expression in Macrophages Through MyD88 Signaling
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DOI：
10.1007/s10753-012-9463-4
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发表时间：
2012-08-01
期刊：
影响因子：
5.1
通讯作者：
Santos, Manuela M.
中科院分区：
文献类型：
--
作者：
Layoun, Antonio;Santos, Manuela M.
铁调素是巨噬细胞铁再循环的关键调节剂，其主要由肝细胞合成，但也由巨噬细胞合成。然而，对铁调素在巨噬细胞中的分子调控知之甚少。在本研究中，我们研究了铁调素在RAW264.7巨噬细胞系和小鼠腹腔巨噬细胞中的调节，这些巨噬细胞用不同的Toll样受体（TLR）配体刺激。我们发现TLR-2和TLR-4配体在RAW264.7细胞和野生型鼠腹腔巨噬细胞中激活铁调素表达，但在从TLR 2（-/-）、TLR-4缺陷或MyD 88（-/-）小鼠分离的鼠腹腔巨噬细胞中不激活。通过用脂多糖（LPS，TLR 4配体）刺激的RAW264.7细胞的IL-6产生通过存在于培养基中的高量的铁而增强。我们的结论是，铁调素在巨噬细胞中的表达调节主要是通过TLR 2和TLR 4受体通过MyD 88依赖性信号通路和铁调素在巨噬细胞中的铁积累的自分泌调节可能会影响促炎细胞因子的产生水平。
Hepcidin is a key regulator of iron recycling by macrophages that is synthesized mainly by hepatocytes but also by macrophages. However, very little is known about the molecular regulation of hepcidin in macrophages. In the present study, we investigated hepcidin regulation in the RAW264.7 macrophage cell line and in murine peritoneal macrophages stimulated with different Toll-like receptor (TLR) ligands. We found that TLR-2 and TLR-4 ligands activated hepcidin expression in RAW264.7 cells and in wild-type murine peritoneal macrophages, but not in murine peritoneal macrophages isolated from TLR2(-/-), TLR-4-deficient or MyD88(-/-) mice. IL-6 production by RAW264.7 cells stimulated with lipopolysaccharide (LPS, TLR4 ligand) was enhanced by high amounts of iron present in the culture medium. We conclude that hepcidin expression in macrophages is regulated mainly through TLR2 and TLR4 receptors via the MyD88-dependent signaling pathway and that autocrine regulation of iron accumulation in macrophages by hepcidin may affect the levels of proinflammatory cytokine production.