SIRT2-PFKP interaction dysregulates phagocytosis in macrophages with acute ethanol-exposure.

ABSTRACT: Alcohol abuse, reported by 1/8^th critically ill patients, is an independent risk factor for death in sepsis. Sepsis kills over 270,000 patients/year in the US. We reported that the ethanol-exposure suppresses innate-immune response, pathogen clearance, and decreases survival in sepsis-mice via sirtuin 2 (SIRT2). SIRT2 is an NAD+-dependent histone-deacetylase with anti-inflammatory properties. We hypothesized that in ethanol-exposed macrophages, SIRT2 suppresses phagocytosis and pathogen clearance by regulating glycolysis. Immune cells use glycolysis to fuel increased metabolic and energy demand of phagocytosis. Using ethanol-exposed mouse bone marrow- and human blood monocyte-derived macrophages, we found that SIRT2 mutes glycolysis via deacetylating key glycolysis

SUBMITTER: Gandhirajan A 

PROVIDER: S-EPMC9972587 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature