Figure 2.

HIF Linking Inflammation and Metabolism. HIF serves as a molecular bridge in the immunoinflammatory and metabolism. On one hand, HIF promotes the activation of immune cells, metabolic reprogramming, and the release of inflammatory mediators. On the other hand, the exposure of immune cells to hypoxia from oxygen-deprived environments at sites of inflammation activates HIF. For example, in the case of macrophages infiltrating HPH, HIF drives the release of cytokines through crosstalk with the NF-κB signaling pathway. This enhances macrophage recruitment, chemotaxis, and polarization. Additionally, in response to hypoxia, mitochondrial oxidative phosphorylation is inhibited while glycolysis is enhanced. This leads to an increased production of ROS and metabolites such as succinate and fumarate by macrophages, which in turn activate and stabilize HIF.