Conclusion
We highlighted that extracellular histone H3 facilitated lipopolysaccharides-induced HUVEC ferroptosis via activating ROS/JNK pathway, and such an effect could be antagonized by E2.
Methods
Clinical sample, cecal ligation and puncture (CLP)-induced animal models and lipopolysaccharides (LPS)-induced cell models were prepared for testing relative expression of extracellular histone H3 and E2 as well as analyzing the role of extracellular histone H3 and E2 in sepsis concerning cell viability, reactive oxygen species (ROS), and ferroptosis.
Results
Under sepsis, we found increased ferroptosis and extracellular histone H3 content, but reduced E2 concentration. Extracellular histone H3 facilitated ferroptosis of human umbilical vein endothelial cells (HUVECs) induced by LPS through activating the ROS/c-Jun N-terminal kinase (JNK) pathway. Moreover, E2 antagonized the effect of extracellular histone H3 on LPS-induced HUVEC ferroptosis and sepsis injury in CLP-induced animal models.