Department of Surgery, University of Michigan, Ann Arbor, Michigan.
Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.
Shock. 2019 Dec;52(6):612-621. doi: 10.1097/SHK.0000000000001312.
Acid aspiration-induced lung injury is a common disease in the intensive care unit (ICU) and acute respiratory distress syndrome (ARDS). Hypoxia-inducible factor (HIF)-1α is a major transcription factor responsible for regulating the cellular response to changes in oxygen tension. A clear understanding of the function of HIF-1α in lung inflammatory response is currently lacking. Here, we sought to determine the role of HIF-1α in type 2 alveolar epithelial cells (AEC) in the generation of the acute inflammatory response following gastric aspiration (GA). GA led to profound hypoxia at very early time points following GA. This correlated to a robust increase in HIF-1α, tissue albumin and pro-inflammatory mediators following GA in AECs. The extent of lung injury and the release of pro/anti-inflammatory cytokines were significantly reduced in HIF-1α (-/-) mice. Finally, we report that HIF-1α upregulation of the acute inflammatory response is dependent on NF-κB following GA.
酸吸入性肺损伤是重症监护病房（ICU）和急性呼吸窘迫综合征（ARDS）中的常见疾病。缺氧诱导因子（HIF）-1α是一种主要的转录因子，负责调节细胞对氧张力变化的反应。目前，对于 HIF-1α 在肺炎症反应中的功能尚不清楚。在这里，我们试图确定 HIF-1α在胃吸入（GA）后急性炎症反应中 2 型肺泡上皮细胞（AEC）中的作用。GA 在 GA 后非常早期导致严重缺氧。这与 GA 后 AEC 中 HIF-1α、组织白蛋白和促炎介质的强烈增加相关。在 HIF-1α（-/-）小鼠中，肺损伤的程度和促炎/抗炎细胞因子的释放明显减少。最后，我们报告 HIF-1α 在 GA 后通过 NF-κB 上调急性炎症反应。
