MST1 modulates inflammatory responses by targeting the NF-κB/NLRP3 pathway in LPS-induced acute lung injury.

Acute lung injury (ALI) represents a severe respiratory condition. Inflammation is a pivotal factor in the pathogenesis of ALI. Mammalian STE20-like protein kinase 1 (MST1) has emerged as a key regulator of sphingolipid metabolism and a mediator of inflammatory responses. However, the precise role and underlying mechanisms of MST1 in lipopolysaccharide (LPS)-induced ALI remain unclear. This study aimed to investigate the influence of MST1 on the inflammatory response in LPS-induced ALI. An LPS-induced ALI model was established using RAW 264.7 cells and mice. In vivo, lung histopathological changes, wet-to-dry (W/D) weight ratio, myeloperoxidase (MPO) activity, and inflammatory cytokine levels [interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α)] were assessed. Oxidative stress markers, including superoxide dismutase (SOD) activity and malondialdehyde (MDA) content, were measured. In vitro, MST1 overexpression was induced in RAW 264.7 cells via lentiviral transfection. Cell viability and proliferation were evaluated using the CCK-8 assay. The expression levels of NF-κB and NLRP3 signaling pathways in vitro or in vivo were analyzed using reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR) and western blotting analysis. The results showed that inhibition of MST1 expression attenuated lung damage, alleviated inflammation, enhanced antioxidant capacity, and inhibited the activation of NF-κB and NLRP3 pathways in vivo. In contrast, MST1 overexpression promoted cell proliferation and inflammation in vitro, accompanied by the activation of NF-κB and NLRP3 signaling pathways. This study demonstrated that MST1 activation contributed to inflammation in LPS-induced ALI by modulating the NF-κB/NLRP3 signaling pathway. Targeting MST1 may represent a novel approach to the treatment of ALI.