Department of Anesthesiology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas
Department of Anesthesiology, The University of Texas Health Science Center at Houston, McGovern Medical School, Houston, Texas.
J Appl Physiol (1985). 2017 Nov 1;123(5):1303-1320. doi: 10.1152/japplphysiol.00101.2017. Epub 2017 Aug 10.
Hypoxic tissue conditions occur during a number of inflammatory diseases and are associated with the breakdown of barriers and induction of proinflammatory responses. At the same time, hypoxia is also known to induce several adaptive and tissue-protective pathways that dampen inflammation and protect tissue integrity. Hypoxia-inducible factors (HIFs) that are stabilized during inflammatory or hypoxic conditions are at the center of mediating these responses. In the past decade, several genes regulating extracellular adenosine metabolism and signaling have been identified as being direct targets of HIFs. Here, we discuss the relationship between inflammation, hypoxia, and adenosine and that HIF-driven adenosine metabolism and signaling is essential in providing tissue protection during inflammatory conditions, including myocardial injury, inflammatory bowel disease, and acute lung injury. We also discuss how the hypoxia-adenosine link can be targeted therapeutically in patients as a future treatment approach for inflammatory diseases.
缺氧组织条件发生在许多炎症性疾病中，并与屏障的破坏和促炎反应的诱导有关。同时，缺氧也被认为能诱导几种适应性和组织保护途径，从而抑制炎症并保护组织完整性。在炎症或缺氧条件下稳定的缺氧诱导因子 (HIFs) 是介导这些反应的中心。在过去的十年中，已经确定了几种调节细胞外腺苷代谢和信号转导的基因是 HIFs 的直接靶标。在这里，我们讨论了炎症、缺氧和腺苷之间的关系，以及 HIF 驱动的腺苷代谢和信号转导在炎症条件下提供组织保护方面的重要性，包括心肌损伤、炎症性肠病和急性肺损伤。我们还讨论了如何在患者中靶向治疗缺氧-腺苷联系，作为炎症性疾病的未来治疗方法。
