Li Xiaojuan, Li Lian, Sun Yu, Wu Jie, Wang Genlin
College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
Cell Stress Chaperones. 2016 May;21(3):439-52. doi: 10.1007/s12192-016-0671-y. Epub 2016 Jan 26.
Lipopolysaccharide (LPS)-binding protein (LBP) plays a crucial role in the recognition of bacterial components, such as LPS that causes an immune response. The aim of this study was to compare the different effects of recombinant bovine wild LBP and mutant LBP (67 Ala → Thr) on the LPS-induced inflammatory response of bovine mammary epithelial cells (BMECs). When BMECs were treated with various concentrations of recombinant bovine lipopolysaccharide-binding protein (RBLBP) (1, 5, 10, and 15 μg/mL) for 12 h, RBLBP of 5 μg/mL increased the apoptosis of BMECs induced by LPS without cytotoxicity, and mutant LBP resulted in a higher cell apoptosis than wild LBP did. By gene-chip microarray and bioinformatics, the data identified 2306 differentially expressed genes that were changed significantly between the LPS-induced inflamed BMECs treated with 5 μg/mL of mutant LBP and the BMECs only treated with 10 μg/mL of LPS (fold change ≥2). Meanwhile, 1585 genes were differently expressed between the inflamed BMECs treated with 5 μg/mL of wild LBP and 10 μg/mL of LPS-treated BMECs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses showed that these differentially expressed genes were involved in different pathways that regulate the inflammation response. It predicted that carriers of this mutation increase the risk for a more severe inflammatory response. Our study provides an overview of the gene expression profile between wild LBP and mutant LBP on the LPS-induced inflammatory response of BMECs, which will lead to further understanding of the potential effects of LBP mutations on bovine mammary glands.
脂多糖(LPS)结合蛋白(LBP)在识别细菌成分(如引发免疫反应的LPS)中起着关键作用。本研究的目的是比较重组牛野生型LBP和突变型LBP(67位丙氨酸→苏氨酸)对LPS诱导的牛乳腺上皮细胞(BMECs)炎症反应的不同影响。当用不同浓度的重组牛脂多糖结合蛋白(RBLBP)(1、5、10和15μg/mL)处理BMECs 12小时时,5μg/mL的RBLBP增加了LPS诱导的BMECs凋亡且无细胞毒性,并且突变型LBP导致的细胞凋亡高于野生型LBP。通过基因芯片微阵列和生物信息学,数据鉴定出2306个差异表达基因,这些基因在经5μg/mL突变型LBP处理的LPS诱导的炎症性BMECs与仅用10μg/mL LPS处理的BMECs之间有显著变化(倍数变化≥2)。同时,在经5μg/mL野生型LBP处理的炎症性BMECs与经10μg/mL LPS处理的BMECs之间有1585个基因差异表达。基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路分析表明,这些差异表达基因参与了调节炎症反应的不同通路。预测该突变携带者增加了发生更严重炎症反应的风险。我们的研究概述了野生型LBP和突变型LBP在LPS诱导的BMECs炎症反应中的基因表达谱,这将有助于进一步了解LBP突变对牛乳腺的潜在影响。