LAUSR

Lipopolysaccharide (LPS) can induce inflammatory responses in piglets, causing immunological stress and tissue damage. However, chronic LPS infection may lead to LPS‐induced immunological stress resistance. The molecular mechanisms underlying LPS stress have not been fully elucidated. Here, we conducted a global comparative proteomics analysis to investigate the molecular regulation of LPS stress using an immunological stress model of weaned piglets. A shotgun‐based SWATH‐MS workflow was used for global proteomes of the piglet livers after 15‐day LPS treatment. Out of 3700 quantified proteins, 93 proteins showed differential changes under LPS stress. Bioinformatics analysis indicated that the differentially expressed proteins were mainly involved in inflammatory response, oxidation‐redox processes and defense reactions, and were enriched in a phagosome pathway. Several key proteins associated with oxidative stress (SOD2), inflammation response (STEAP4 and S100 family) and the phagosome pathway were verified by activity and targeted‐MS analyses. The observed responses appear to mitigate hepatic damage due to excessive oxidative stress, inflammation, and repression of the phagosome pathway. Our results reveal that an increased STEAP4 expression in piglets appears involved in cellular regulation by LPS stress and subsequent immunological stress resistance. This study sheds new light on the mechanism of prevention and relieving injury by LPS‐induced immune responses.