State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, Beijing, P. R. China.
Institute of Biotechnology, Cornell University, Ithaca, NY, USA.
Electrophoresis. 2018 Sep;39(18):2321-2331. doi: 10.1002/elps.201700467. Epub 2018 May 28.
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.
脂多糖（LPS）可诱导仔猪产生炎症反应，引起免疫应激和组织损伤。然而，慢性 LPS 感染可能导致 LPS 诱导的免疫应激抵抗。LPS 应激的分子机制尚未完全阐明。在这里，我们使用断奶仔猪免疫应激模型进行了全局比较蛋白质组学分析，以研究 LPS 应激的分子调控。使用基于 shotgun 的 SWATH-MS 工作流程对 LPS 处理 15 天后仔猪肝脏的全蛋白质组进行了分析。在 3700 种定量蛋白质中，有 93 种蛋白质在 LPS 应激下发生差异变化。生物信息学分析表明，差异表达的蛋白质主要参与炎症反应、氧化还原过程和防御反应，并富集在吞噬体途径中。通过活性和靶向-MS 分析验证了与氧化应激（SOD2）、炎症反应（STEAP4 和 S100 家族）和吞噬体途径相关的几个关键蛋白。观察到的反应似乎减轻了由于过度氧化应激、炎症和吞噬体途径抑制引起的肝损伤。我们的研究结果表明，仔猪中 STEAP4 表达的增加似乎参与了 LPS 应激的细胞调节以及随后的免疫应激抵抗。本研究为 LPS 诱导的免疫反应引起的预防和缓解损伤的机制提供了新的见解。
