The Role and Potential Regulatory Mechanism of <i>STING</i> Modulated Macrophage Apoptosis and Differentiation in Severe Acute Pancreatitis-Associated Lung Injury

Abstract

This study aims to investigate the role of STING in promoting macrophage apoptosis and regulating macrophage polarization in severe acute pancreatitis (SAP)-associated lung injury <i>in vitro</i> and <i>in vivo</i>. A murine model was established by intraperitoneal injection of caerulein and lipopolysaccharide (LPS). Meanwhile, ANA-1 cells were stimulated with LPS to induce apoptosis <i>in vitro</i>. More primary alveolar macrophages underwent apoptosis and M1 macrophage polarization in the SAP group compared with the control group, which was reversed by inhibiting STING. When ANA-1 cells were induced into M2-type macrophages, the reduction of M1 macrophage markers was accompanied by a decrease of LPS-induced apoptosis. Finally, the inhibitory effect of C-176 on STING ameliorates lung injury and inflammation by adjusting macrophage polarization and rescuing apoptosis. Therefore, inhibiting STING could be a new therapeutic strategy for treating acute pancreatitis-associated lung injury.