Modulating Glutamine Metabolism Reprograms Pro-Inflammatory Differentiation in Macrophages.

ABSTRACT: Previous in vivo studies demonstrated that JHU083/DON, a glutamine analog drug, potently reprograms M1/M2 macrophages. To determine whether these effects are direct or indirect, we utilized an in vitro murine bone marrow-derived macrophage (BMDM) model, which recapitulates macrophage differentiation and polarization processes, to examine the impact of DON on the M1 macrophages. DON was applied during M1 differentiation or to fully polarized M1 macrophages, revealing that glutamine inhibition initially suppressed M1 activity but later enhanced it, resulting in sustained pro-inflammatory activation. Multi-omics analyses (bulk RNA-seq and LC-MS), time-course assays, and glutamine depletion experiments consistently suggested that prolonged glutamine inhibition elevates glutamine levels, which

SUBMITTER: Qi S 

PROVIDER: S-EPMC12458286 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature