炎症中的缺氧诱导因子1α（HIF1α）与代谢重编程
HIF1α and metabolic reprogramming in inflammation.
作者信息
Corcoran Sarah E, O'Neill Luke A J
出版信息
J Clin Invest. 2016 Oct 3;126(10):3699-3707. doi: 10.1172/JCI84431. Epub 2016 Aug 29.
Abstract
HIF1α is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction involves succinate, which inhibits prolyl hydroxylases (PHDs). Pyruvate kinase M2 (PKM2) is also induced and interacts with and promotes the function of HIF1α. In another critical inflammatory cell type, Th17 cells, HIF1α acts via the retinoic acid-related orphan receptor-γt (RORγt) to drive Th17 differentiation. HIF1α is therefore a key reprogrammer of metabolism in inflammatory cells that promotes inflammatory gene expression.
摘要
低氧诱导因子1α（HIF1α）是参与细胞代谢调控途径的常见成分，在调节免疫细胞效应功能中发挥作用。此外，HIF1α对树突状细胞的成熟和T细胞的激活至关重要。HIF1α在脂多糖（LPS）激活的巨噬细胞中被诱导，它在糖酵解和促炎基因（特别是Il1b）的诱导中起关键作用。LPS刺激诱导HIF1α的机制涉及琥珀酸，它抑制脯氨酰羟化酶（PHD）。丙酮酸激酶M2（PKM2）也被诱导，并与HIF1α相互作用并促进其功能。在另一种关键的炎症细胞类型——辅助性T细胞17（Th17）细胞中，HIF1α通过视黄酸相关孤儿受体γt（RORγt）发挥作用，驱动Th17分化。因此，HIF1α是炎症细胞代谢的关键重编程因子，可促进炎症基因表达。
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