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首页> 外文期刊>Infection and immunity >Hypoxia-Inducible Factor 1-Regulated Lysyl Oxidase Is Involved in Staphylococcus aureus Abscess Formation
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Hypoxia-Inducible Factor 1-Regulated Lysyl Oxidase Is Involved in Staphylococcus aureus Abscess Formation

机译：低氧诱导因子1调节的赖氨酰氧化酶参与金黄色葡萄球菌脓肿的形成。

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Hypoxia-inducible factor 1 (HIF-1) is the key transcription factor involved in the adaptation of mammals to hypoxia and plays a crucial role in cancer angiogenesis. Recent evidence suggests a leading role for HIF-1 in various inflammatory and infectious diseases. Here we describe the role of HIF-1 in Staphylococcus aureus infections by investigating the HIF-1-dependent host cell response. For this purpose, transcriptional profiling of HIF-1α-deficient HepG2 and control cells, both infected with Staphylococcus aureus, was performed. Four hours after infection, the expression of 190 genes, 24 of which were regulated via HIF-1, was influenced. LOX (encoding lysyl oxidase) was one of the upregulated genes with a potential impact on the course of S. aureus infection. LOX is an amine oxidase required for biosynthetic cross-linking of extracellular matrix components. LOX was upregulated in vitro in different cell cultures infected with S. aureus and also in vivo, in kidney abscesses of mice intravenously infected with S. aureus and in clinical skin samples from patients with S. aureus infections. Inhibition of LOX by β-aminopropionitrile (BAPN) did not affect the bacterial load in kidneys or blood but significantly influenced abscess morphology and collagenization. Our data provide evidence for a crucial role of HIF-1-regulated LOX in abscess formation.
机译：缺氧诱导因子1（HIF-1）是参与哺乳动物适应缺氧的关键转录因子，在癌症血管生成中起着至关重要的作用。最近的证据表明，HIF-1在各种炎症和感染性疾病中起着主导作用。在这里，我们通过调查依赖HIF-1的宿主细胞反应来描述HIF-1在金黄色葡萄球菌感染中的作用。为此，对感染了金黄色葡萄球菌的HIF-1α缺陷型HepG2和对照细胞进行转录分析。感染后四个小时，影响了190个基因的表达，其中24个是通过HIF-1调控的。 LOX （编码赖氨酰氧化酶）是上调基因之一，可能对金黄色葡萄球菌感染过程有潜在影响。 LOX是细胞外基质成分生物合成交联所需的胺氧化酶。在金黄色葡萄球菌感染的不同细胞培养物中，以及在体外，它们的体内，，在静脉注射金黄色葡萄球菌感染的小鼠的肾脓肿和临床皮肤样本中，LOX均被上调金黄色葡萄球菌感染的患者。 β-氨基丙腈（BAPN）抑制LOX不会影响肾脏或血液中的细菌负荷，但会显着影响脓肿的形态和胶原蛋白的形成。我们的数据提供了证据，证明了HIF-1调节的LOX在脓肿形成中的关键作用。

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