Phosphoglycerate dehydrogenase-mediated serine reprogramming aggravates macrophage hyperinflammation in murine Pseudomonas aeruginosa pneumonia - PubMed
11 hours ago
- #macrophage inflammation
- #metabolic reprogramming
- #Pseudomonas aeruginosa
- Phosphoglycerate dehydrogenase (PHGDH) plays a key role in macrophage inflammation during Pseudomonas aeruginosa infection.
- Inhibition of PHGDH reduces macrophage hyperactivation and pro-inflammatory cytokine production.
- Myeloid-specific deletion of PHGDH improves survival, reduces lung injury, and lowers bacterial load in mice with Pseudomonas aeruginosa pneumonia.
- Dietary L-serine restriction also improves outcomes in infected mice.
- PHGDH enhances L-serine synthesis, boosting one-carbon metabolism and influencing histone H3 lysine 27 trimethylation and dual-specificity phosphatase 4 interaction.
- This metabolic-epigenetic crosstalk promotes extracellular signal-regulated kinase 1/2 phosphorylation, amplifying inflammation.
- Metabolic modulation is proposed as a potential therapeutic strategy for bacterial pneumonia.