Abstract B08: Metabolic adaption in inflammatory macrophages through the modulation of Fe-S cluster biogenesis factors

Macrophages are among the most abundant normal cells in the tumor microenvironment, and the mechanistic overlap in the metabolic changes in glycolytic cancer cells and inflammatory immune cells suggest that insights into the mechanisms underlying the metabolic changes could be useful in the treatment of both cancers and inflammatory diseases. Metabolic choices in immune cells are tightly linked to cell fate and function. Inflammatory immune cells, such as M1 macrophages and T-helper 17 cells, undergo a shift from OXPHOS to enhanced glucose uptake, glycolysis and the pentose phosphate pathway, whereas anti-inflammatory cells, such as M2 macrophages and regulatory T cells have lower glycolytic rates and higher levels of oxidative metabolism. The metabolic switch from OXPHOS to aerobic glycolysis (Warburg effect) in Toll-like receptor (TLR)-stimulated myeloid cells has been shown to result from the activation of glycolysis through the action of AKT and HIF-1α signaling, with mitochondrial respiration passively decreasing due to NF-kB mediated induction of inducible nitric oxide synthase (iNOS), which produces the toxic gas nitric oxide that damages the Fe-S cluster cofactors that are essential for mitochondrial electron transport. The results reported here indicate that the pro-inflammatory activation of macrophages also involved the active suppression of mitochondrial pyruvate catabolism and respiration through the down-regulation of several genes in the Fe-S cluster biog...
Source: Molecular Cancer Research - Category: Cancer & Oncology Authors: Tags: Signaling Pathways and Cancer Metabolism: Poster Presentations - Proffered Abstracts Source Type: research