Temporal Control of Macrophage Pro-inflammatory Phenotype by a Biphasic HIF-1α Regulatory Program

ABSTRACT: Hypoxia-inducible factor 1α (HIF-1α) broadly orchestrates metabolic reprogramming in inflammatory macrophages. However, how HIF-1α is activated in the earliest events following pattern recognition receptor activation remains unclear. We found that HIF-1α is functionally active shortly after macrophage inflammatory stimulation via a Rubicon (RUBCN)-NADPH-oxidase (NOX2) reactive oxygen species (ROS) axis, driving glycolysis, cytokine production, and bacterial killing before increased protein accumulation. Early HIF-1α stabilization primes inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production, which subsequently suppresses electron transport chain function and induces mitochondrial dysfunction independently of RUBCN. These findings elucidate a temporally-coordina

INSTRUMENT(S): DNBSEQ-G400, Qiagen RNAeasy, Bioanalyzer QubitFluorometer, Agilent 2100, RNA Pico 6000 chip

ORGANISM(S): Mus musculus

SUBMITTER: Jay Cao 

PROVIDER: E-MTAB-16172 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress