J Leukoc Biol. 2025 Apr 17:qiaf047. doi: 10.1093/jleuko/qiaf047. Online ahead of print.
ABSTRACT
Bone marrow-derived dendritic cell (BMDC) activation is associated with rewiring of cellular metabolism and concurrent large-scale changes in gene expression promoting a pro-inflammatory program characterized by expression of inducible nitric oxide synthase (iNOS) and the production of nitric oxide (NO). NO inhibits vital cellular activities including mitochondrial respiration. Mitochondrial respiration inhibition via NO occurs at discrete levels of activating stimulus, termed the mitochondrial respiration threshold, and regulation of this threshold is not fully understood. In this work, we characterize the role of UDP-glucose as a modulator of NO-mediated mitochondrial respiration inhibition via P2Y14 receptor signaling in stimulated BMDCs. We demonstrate BMDCs exhibit an enhanced pro-inflammatory profile in the presence of UDP-glucose, providing evidence for a new NO-regulatory axis in BMDCs. These studies highlight the importance of the growing body of literature supporting metabolites as signaling molecules in activating conditions thus allowing for better modeling of physiologically-relevant contexts for myeloid cell encounters with microbial stimuli.
PMID:40241651 | DOI:10.1093/jleuko/qiaf047