IL-27 Aggravates Sepsis-Induced ARDS by Driving Macrophage Ferroptosis Through Activation of NCOA4-Mediated Ferritinophagy - PubMed
3 days ago
- #Sepsis
- #Ferroptosis
- #ARDS
- IL-27 worsens sepsis-induced ARDS by promoting macrophage ferroptosis via NCOA4-mediated ferritinophagy.
- Study uses wild-type and IL-27 receptor knockout mice to model sepsis, showing IL-27's role in exacerbating lung injury.
- IL-27 combined with LPS enhances ferritinophagy, leading to FTH1 degradation and increased ferroptosis markers.
- NCOA4 degrader CV3 inhibits ferritinophagy, reduces ferroptosis, and mitigates inflammation in sepsis models.
- IL-27R-/- mice resist IL-27-induced lung injury, confirming the specificity of IL-27's pathogenic role.
- Targeting NCOA4-mediated ferritinophagy with CV3 presents a potential therapeutic strategy for sepsis-induced ARDS.