Hypoxia inducible factor-1α is an important regulator of macrophage biology

Hypoxia-inducible factor-1 (HIF-1), a heterodimeric transcription factor composed of the alpha and beta subunits, regulates cellular adaptive responses to hypoxia. Macrophages, which are derived from monocytes, function as antigen-presenting cells that activate various immune responses. HIF-1 alpha regulates the immune response, viability, migration, phenotypic plasticity, and metabolism of macrophages. Specifically, macrophage-derived HIF-1 alpha can prevent excessive pro-inflammatory responses by attenuating the transcriptional activity of nuclear factor-kappa B in vivo and in vitro. HIF-1 alpha modulates macrophage migration by inducing the release of various chemokines and providing necessary energy. HIF-1 alpha promotes macrophage M1 polarization by targeting glucose metabolism. Additionally, HIF-1 alpha induces the upregulation of glycolysis-related enzymes and intermediates of the tricarboxylic acid cycle and pentose phosphate pathway. HIF-1 alpha promotes macrophage apoptosis, necroptosis and reduces autophagy. The current review highlights the mechanisms associated with the regulation of HIF-1 alpha stabilization in macrophages as well as the role of HIF-1 alpha in modulating the physiological functions of macrophages.