Acute lung injury (ALI), a progressive
lung disease mostly caused by
sepsis, is characterized by uncontrolled inflammatory responses, increased oxidative stress, pulmonary barrier dysfunction, and
pulmonary edema.
Ursodeoxycholic acid (UDCA) is a natural
bile acid with various pharmacological properties and is extensively utilized in clinical settings for the management of hepatobiliary ailments. Nonetheless, the potential protective effects and mechanism of UDCA on
sepsis-induced
lung injuries remain unknown. In this study, we reported that UDCA effectively inhibited
pulmonary edema, inflammatory cell infiltration, pro-inflammatory
cytokines production, and oxidative stress. Furthermore, UDCA treatment significantly alleviated the damage of pulmonary barrier and enhanced alveolar fluid clearance. Importantly, UDCA treatment potently suppressed PANoptosis-like cell death which is demonstrated by the block of apoptosis, pyroptosis, and necroptosis. Mechanistically, UDCA treatment prominently inhibited
STING pathway. And the consequential loss of
STING substantially impaired the beneficial effects of UDCA treatment on the inflammatory response, pulmonary barrier, and PANoptosis. These results indicate that
STING plays a pivotal role in the UDCA treatment against
sepsis-induced
lung injury. Collectively, our findings show that UDCA treatment can ameliorate
sepsis-induced
lung injury and verified a previously unrecognized mechanism by which UDCA alleviated
sepsis-induced
lung injury through blocking PANoptosis-like cell death via
STING pathway.