de Jonge Jonathan D, Pennings Jeroen L A, Baken Kirsten A, Konings Joke, Ezendam Janine, Van Loveren Henk
University Maastricht, Nutrition and Toxicology Research Institute Maastricht, Department of Health Risk Analysis and Toxicology, Maastricht, Netherlands.
J Immunotoxicol. 2008 Oct;5(4):385-94. doi: 10.1080/15476910802586126.
New techniques are needed to broaden the understanding of the food allergic response. The capacity of peanut extract to influence gene expression profiles was investigated in a Brown Norway rat model for food allergy. Brown Norway rats were sensitized to peanut extract (0, 1 and 10 mg/rat/d) by daily oral gavage and were dissected after 3, 7 or 14 days of exposure. RNA extracted from mesenteric lymph nodes of individual rats were hybridized against a common reference pool on Agilent whole rat genome (4*44k) arrays. The raw data were normalized and statistically analyzed using the statistical program R. A False Discovery Rate of 10% and a Fold Ratio of - 1.5 < or = Fold Ratio or Fold Ratio > or = 1.5 between the experimental groups and their respective control groups were applied. Differentially expressed genes were clustered into a heatmap. Functional annotation and GeneOntology term enrichment were examined. Furthermore, the involvement of the differentially expressed genes in specific cellular pathways was investigated with MetaCore. Gene expression changes, which were both dose- and time-dependent, were detected after sensitization to peanut. A total of 64 genes were differentially expressed, of which 60 were up-regulated and four were down-regulated. These changes were related to the regulation of immunological processes, most notably increased cell division. The findings indicate that responses to peanut include proliferation of immunologically relevant tissues, which can be identified by analysis of gene expression profiles. This may lay a basis for further research into possibilities for discrimination of allergenic from non-allergenic proteins.
需要新技术来拓宽对食物过敏反应的理解。在棕色挪威大鼠食物过敏模型中研究了花生提取物影响基因表达谱的能力。通过每日口服灌胃使棕色挪威大鼠对花生提取物（0、1和10毫克/大鼠/天）致敏，并在暴露3、7或14天后进行解剖。从个体大鼠的肠系膜淋巴结中提取的RNA与安捷伦全大鼠基因组（4×44k）阵列上的共同参考池进行杂交。使用统计程序R对原始数据进行归一化和统计分析。应用10%的错误发现率以及实验组与其各自对照组之间的-1.5≤倍比或倍比≥1.5。将差异表达基因聚类成热图。检查功能注释和基因本体术语富集情况。此外，使用MetaCore研究差异表达基因在特定细胞途径中的参与情况。致敏花生后检测到基因表达变化，这些变化具有剂量和时间依赖性。总共64个基因差异表达，其中60个上调，4个下调。这些变化与免疫过程的调节有关，最显著的是细胞分裂增加。研究结果表明，对花生的反应包括免疫相关组织的增殖，这可以通过基因表达谱分析来识别。这可能为进一步研究区分变应原性蛋白和非变应原性蛋白的可能性奠定基础。
