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12:03
In Vivo Model for Testing Effect of Hypoxia on Tumor Metastasis
Published on: December 9, 2016
In vitro study: HIF-1α-dependent glycolysis enhances NETosis in hypoxic conditions
Yi Ye1,2,3, Yanjun Wang1,2,3,4, Qiying Xu1,2,3,5
1Research Center for High Altitude Medicine, Qinghai University, Xining, China.
Frontiers in Immunology
|May 13, 2025
Summary
Hypoxia-inducible factor (HIF)-1α-driven glycolysis boosts neutrophil extracellular trap (NET) formation under low oxygen. Inhibiting HIF-1α or glycolysis reduces NETosis, highlighting metabolic reprogramming
Area of Science:
- Immunology
- Metabolic pathways
- Cellular stress response
Background:
- Hypoxia significantly impacts immune responses, particularly in neutrophils.
- Hypoxia-inducible factor (HIF)-1α regulates metabolism and inflammation.
- The role of HIF-1α-dependent glycolysis in NETosis under hypoxia is not well understood.
Purpose of the Study:
- To investigate the role of HIF-1α in regulating glycolysis and its effect on NETosis in neutrophils under hypoxic conditions.
- To explore the impact of metabolic reprogramming on neutrophil function during hypoxia.
Main Methods:
- Utilized human neutrophils and dHL-60 cell models.
- Employed western blotting, immunofluorescence, ELISA, and flow cytometry.
- Investigated the effects of HIF-1α inhibition (LW6) and glycolytic blockade (Bay-876).
Main Results:
- HIF-1α-dependent glycolysis upregulates key glycolytic enzymes, enhancing NETosis under hypoxia.
- Inhibiting HIF-1α with LW6 significantly reduced NETosis.
- Blocking glycolysis with Bay-876 also markedly decreased NETosis.
Conclusions:
- HIF-1α-dependent glycolysis is a key driver of NET formation during hypoxic stress.
- Metabolic reprogramming is crucial for neutrophil function in hypoxia.
- Targeting metabolic pathways may offer therapeutic strategies for hypoxia-associated inflammatory diseases.
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