Interferon Gamma Induces Reversible Metabolic Reprogramming of M1 Macrophages to Sustain Cell Viability and Pro-Inflammatory Activity.

ABSTRACT: Classical activation of M1 macrophages with lipopolysaccharide (LPS) is associated with a metabolic switch from oxidative phosphorylation to glycolysis. However, the generalizability of such metabolic remodeling to other modes of M1 macrophage stimulation, e.g. type II interferons (IFNs) such as IFNγ, has remained unknown as has the functional significance of aerobic glycolysis during macrophage activation. Here we demonstrate that IFNγ induces a rapid activation of aerobic glycolysis followed by a reduction in oxidative phosphorylation in M1 macrophages. Elevated glycolytic flux sustains cell viability and inflammatory activity, while limiting reliance on mitochondrial oxidative metabolism. Adenosine triphosphate (ATP) distributed by aerobic glycolysis is critical for sustaining IFN-γ tri

SUBMITTER: Wang F 

PROVIDER: S-EPMC5953001 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature