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Pharmacological Inhibition Of Hif-1 Alpha And Its Effects On Dendritic Cell Metabolic Reprogramming
Sahene, Warrick
Sahene, Warrick
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Abstract
Dendritic cells (DCs) are antigen presenting cells (APCs), a subtype of immune cells that present cellular information to T cells in the immune system. Hypoxia inducible factor 1 alpha (HIF-1 alpha) is an important transcription factor that facilitates dendritic cell metabolism by upregulating glycolysis in activated DCs. In this project, we examined the effects of HIF-1 alpha inhibition on metabolic processes of dendritic cells. Using techniques such as flow cytometry, western blotting, and extracellular flux analyzers, we used a selective inhibitor of HIF-1 alpha to test the hypothesis that HIF-1 alpha promotes glycolytic dependent processes such as glucose production, survival, and maturation. The results revealed that HIF-1 alpha impacts oxygen consumption rates in DCs, but does not affect survival, maturation rates, and glycolytic rates under the conditions studied. Dendritic cell secretion of IL-12, a proinflammatory cytokine upregulated during metabolism, decreased in a dose dependent manner under HIF-1 alpha inhibition. Understanding the effects of HIF-1 alpha can provide insight on how dendritic cells utilize their fuel source to facilitate immunological tasks and how in the future, we can optimize these sources to improve immune system functionality.
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2020-01-01