PKM2 Promotes Glycolysis in Alveolar Macrophages and Induces Inflammation in Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a common complication in premature infants, characterized by an overactive inflammatory response in the lungs. Alveolar macrophages (AMs) play a crucial role in BPD, promoting autoimmune tissue inflammation by releasing various bioactive substances such as IL-1β and TNF-α. The inflammatory state of macrophages is significantly influenced by the metabolic environment. Glycolysis supports the polarization of macrophages to the M1 phenotype and the key enzyme pyruvate kinase M2 (PKM2) can regulate macrophage polarization in various disease models and is associated with inflammatory response. However, the effect of PKM2 on alveolar macrophages in the hyperoxia-induced BPD model remains unclear. In this study, we aim to investigate the role of PKM2 in glycolysis in influencing the pro-inflammatory response of M1 alveolar macrophages in BPD model. By establishing high-oxygen-induced BPD mouse and MH-S cell models, the relationship between glycolysis and the excessive activation of pro-inflammatory responses in alveolar macrophages was verified. 2-Deoxy-D-glucose (2-DG) and shikonin were applied in vitro and in vivo to investigate the impact of intervention on glycolysis and PKM2 on M1 alveolar macrophage inflammatory ability. The results show that hyperoxia induces lung injury in BPD mice. PKM2 regulates the level of glycolysis to affect the inflammatory level of BPD, and is accompanied by a change in the polarization level of M1 alveolar macrophages. By inhibiting the activity of PKM2, shikonin reduces the activation level of M1 alveolar macrophages, weaken the pro-inflammatory response, and alleviate lung injury. This provides a new idea for the clinical treatment of BPD.