Department of Molecular Biology and Genetics, Faculty of Science and Technology, Aarhus University, Tjele, Denmark.
Physiol Genomics. 2012 Jun 1;44(11):595-606. doi: 10.1152/physiolgenomics.00084.2011. Epub 2012 Apr 10.
The mammalian liver works to keep the body in a state of homeostasis and plays an important role in systemic acute phase response to infections. In this study we investigated the bovine hepatic acute phase response at the gene transcription level in dairy cows with experimentally Escherichia coli-induced mastitis. At time = 0, each of 16 periparturient dairy cows received 20-40 colony-forming units of live E. coli in one front quarter of the udder. A time series of liver biopsies was collected at -144, 12, 24, and 192 h relative to time of inoculation. Changes in transcription levels in response to E. coli inoculation were analyzed using the Bovine Genome Array and tested significant for 408 transcripts over the time series [adjusted p ≤ 0.05, abs(fold-change) > 2]. After 2-D clustering, transcripts represented three distinct transcription profiles: 1) regulation of gene transcription and apoptosis, 2) responses to cellular stress invoked by reactive metabolites, and 3) metabolism and turnover of proteins. The results showed that the liver went through a period of perturbations to its normal homeostatic condition during the first 24 h following the E. coli-induced intra-mammary inflammation. In previous studies, bacterial lipopolysaccharide, LPS, was used for intramammary stimulation to mimic E. coli infection. Comparing responses to LPS and E. coli, induced biochemical processes were similar but not identical (94 and 85% similarity between corresponding samples at early and late acute phase, respectively), but their kinetics were not. A notable difference concerned transcription of factors associated with oxidative stress in E. coli-induced liver responses.
哺乳动物的肝脏致力于维持身体的内稳态，并在系统性急性感染反应中发挥重要作用。在本研究中，我们研究了实验性大肠杆菌诱导乳腺炎奶牛的肝脏基因转录水平的牛肝脏急性期反应。在时间 = 0 时，每头围产期奶牛的 16 头前乳房接受了 20-40 个活大肠杆菌的菌落形成单位。在接种时间的 -144、12、24 和 192 小时，采集了一系列肝活检。使用牛基因组芯片分析了对大肠杆菌接种的转录水平变化，并在时间序列上对 408 个转录本进行了显著测试[调整后的 p ≤ 0.05，abs（fold-change）> 2]。经过 2-D 聚类，转录本代表了三种不同的转录谱：1）基因转录和细胞凋亡的调节，2）活性代谢物引起的细胞应激反应，3）蛋白质的代谢和周转。结果表明，在大肠杆菌诱导的乳腺炎后 24 小时内，肝脏经历了一个正常内稳态条件的波动期。在以前的研究中，细菌脂多糖，LPS，被用于乳腺内刺激以模拟大肠杆菌感染。比较 LPS 和大肠杆菌的反应，诱导的生化过程相似但不完全相同（早期和晚期急性期的对应样本之间的相似性分别为 94%和 85%），但它们的动力学不同。一个显著的区别是与大肠杆菌诱导的肝脏反应中氧化应激相关的转录因子。
