FCER1G-Notch1 mediated M1 macrophages polarization and pancreatic acinar cells death in acute pancreatitis.

Acute pancreatitis (AP) is a digestive system disorder characterized by overactivation of pancreatic enzymes within the pancreas, leading to severe pathological features. M1 macrophage activation and subsequent pro-inflammatory responses are essential in AP development. Investigating macrophage polarization during AP can help further elucidate the pathogenesis of AP and provide theoretical foundations and therapeutic strategies for AP. In this study, we found that FCER1G expression and Notch1 activity were up-regulated in LPS-induced M1 macrophages. FCER1G and Notch1 knockdown could inhibit LPS-induced inflammation in M1 macrophages and pancreatic acinar cell (PAC) damage, indicating the vital functions of FCER1G and Notch1 in M1 macrophage polarization. Further research indicated that FCER1G promotes M1 macrophage polarization and PAC damage by regulating, rather than enhancing, interactions with Notch1 in LPS-induced M1 macrophages. Finally, we showed that inhibition of FCER1G could alleviate AP injury through the Notch1 pathway in mice, providing a novel intervention target for AP therapy.