S100A16 as a potential therapeutic target in sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI) is a major contributor to mortality in critically ill patients, yet its molecular basis remains incompletely understood. In this study, we found that S100A16 was significantly upregulated in the lungs of septic mice and in the serum of sepsis patients, with expression levels correlating with disease severity. We further provided evidence that S100A16 directly interacts with S100A11 and that the two proteins show reciprocal regulation. Functionally, knockdown of either protein in a murine sepsis model attenuated lung injury, reduced neutrophil infiltration, and improved survival. In vitro experiments showed that S100A16 overexpression increased endoplasmic reticulum (ER) stress-related markers in lung epithelial cells. Furthermore, the protective effects of S100A16 knockdown were partially counteracted by S100A11 overexpression. These results indicate that the S100A16-S100A11 axis represents one of the contributing factors in sepsis-induced ALI and support the potential therapeutic relevance of this axis.