Upon LPS stimulation, macrophages undergo metabolic reprogramming to enhance glycolysis with suppressed oxidative metabolism, which further increased succinate accumulation and SDH activity to boost inflammatory response. Tan-IIA remarkably inhibited mitochondrial ROS generation through interrupting SDH hyperactivation to further reduce HIF-1α stabilization and transcription. And for that, attenuated glycolysis and preserved Sirt2 activity contributed to suppression of NLRP3 inflammatory activation to further reduce the maturation of IL-1β.
- Qiu-yan Liu
- Yu Zhuang
- Zhi-xia Qiu
