HIF-mediated innate immune responses: cell signaling and therapeutic implications.
HIF-mediated innate immune responses: cell signaling and therapeutic implications.
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DOI：
10.2147/hp.s50269
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Walmsley SR
中科院分区：
文献类型：
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作者：
Harris AJ;Thompson AR;Whyte MK;Walmsley SR
在免疫反应中，被感染、受损或发炎组织吸收的白细胞必须适应比循环中低得多的氧气水平。缺氧诱导因子（hif）是细胞对缺氧反应的关键介质，与其他细胞类型一样，hif对糖酵解的上调至关重要，糖酵解使先天免疫细胞能够厌氧产生三磷酸腺苷。越来越多的证据表明，缺氧也调节许多其他先天免疫功能，包括细胞迁移、细胞凋亡、病原体吞噬、抗原呈递和细胞因子、趋化因子、血管生成和抗菌因子的产生。许多这些功能都是由hif介导的，hif不仅在翻译后通过缺氧稳定，而且在炎症信号的作用下转录上调。在这里，我们回顾了hif在先天免疫细胞对缺氧的反应中的作用，无论是体外还是体内，特别关注骨髓细胞，迄今为止大多数研究都是在骨髓细胞上进行的。
Leukocytes recruited to infected, damaged, or inflamed tissues during an immune response must adapt to oxygen levels much lower than those in the circulation. Hypoxia inducible factors (HIFs) are key mediators of cellular responses to hypoxia and, as in other cell types, HIFs are critical for the upregulation of glycolysis, which enables innate immune cells to produce adenosine triphosphate anaerobically. An increasing body of evidence demonstrates that hypoxia also regulates many other innate immunological functions, including cell migration, apoptosis, phagocytosis of pathogens, antigen presentation and production of cytokines, chemokines, and angiogenic and antimicrobial factors. Many of these functions are mediated by HIFs, which are not only stabilized posttranslationally by hypoxia, but also transcriptionally upregulated by inflammatory signals. Here, we review the role of HIFs in the responses of innate immune cells to hypoxia, both in vitro and in vivo, with a particular focus on myeloid cells, on which the majority of studies have so far been carried out.