Caspase-11-mediated non-canonical pyroptosis is a key mechanism of alveolar epithelial cell injury in LPS-induced ARDS

Abstract

Alveolar epithelial cells (AECs) injury is a critical event in the pathogenesis of acute respiratory distress syndrome (ARDS); however, the underlying mechanisms remain complex, and it is still unclear which cell death or inflammatory pathway predominates. In this study, we analyzed transcriptomic data from primary AECs in ARDS and compared the enrichment levels of six cell death pathways, and found that pyroptosis was the most significantly altered pathway. Subsequently, we validated these findings using a mouse model of ARDS and an in vitro LPS transfection model, and demonstrated that AECs pyroptosis is primarily mediated by Caspase-11. Furthermore, we optimized the conditions for LPS transfection to establish a model of non-canonical pyroptosis in AECs. Collectively, these results indicate that Caspase-11‑mediated non‑canonical pyroptosis is an important mechanism of AECs destruction in ARDS, and provide a new strategy for targeted therapy.