缺氧诱导因子-1α与传染病：新疗法开发的新前沿
HIF-1alpha and infectious diseases: a new frontier for the development of new therapies.
作者信息
Santos Sânia Alves Dos, Andrade Dahir Ramos de
机构信息
Universidade de São Paulo, Instituto de Medicina Tropical de São Paulo, Laboratório de Bacteriologia (LIM 54), São Paulo, São Paulo, Brazil.
出版信息
Rev Inst Med Trop Sao Paulo. 2017 Dec 21;59:e92. doi: 10.1590/S1678-9946201759092.
Abstract
The aim of this review is to show the significant role of HIF-1alpha in inflammatory and infectious diseases. Hypoxia is a physiological characteristic of a wide range of diseases from cancer to infection. Cellular hypoxia is sensed by oxygen-sensitive hydrolase enzymes, which control the protein stability of hypoxia-inducible factor alpha 1 (HIF-1alpha) transcription factors. When stabilized, HIF-1alpha binds with its cofactors to HIF-responsive elements (HREs) in the promoters of target genes to organize a broad ranging transcriptional program in response to the hypoxic environment. HIF-1alpha also plays a regulatory function in response to a diversity of molecular signals of infection and inflammation even under normoxic conditions. HIF-1alpha is stimulated by pro-inflammatory cytokines, growth factors and a wide range of infections. Its induction is a general element of the host response to infection. In this review, we also discuss recent advances in knowledge on HIF-1alpha and inflammatory responses, as well as its direct influence in infectious diseases caused by bacteria, virus, protozoan parasites and fungi.
摘要
本综述的目的是展示缺氧诱导因子-1α（HIF-1α）在炎症性疾病和感染性疾病中的重要作用。缺氧是从癌症到感染等多种疾病的生理特征。细胞缺氧由氧敏感水解酶感知，这些酶控制缺氧诱导因子α1（HIF-1α）转录因子的蛋白质稳定性。当HIF-1α稳定时，它与其辅因子结合到靶基因启动子中的缺氧反应元件（HRE）上，以响应缺氧环境组织广泛的转录程序。即使在常氧条件下，HIF-1α在响应感染和炎症的多种分子信号时也发挥调节功能。HIF-1α受到促炎细胞因子、生长因子和多种感染的刺激。其诱导是宿主对感染反应的一个普遍因素。在本综述中，我们还讨论了关于HIF-1α和炎症反应的最新知识进展，以及它对由细菌、病毒、原生动物寄生虫和真菌引起的感染性疾病的直接影响。
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