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Analysis of the effect of stress on the gut-associated immune systems by the genetic method

用遗传学方法分析应激对肠道相关免疫系统的影响

基本信息

批准号：
12670388
负责人：
NAKANO Yumiko
金额：
$ 2.18万
依托单位：
Osaka Prefectural Institute of Public Health
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2000
资助国家：
日本
起止时间：
2000 至 2002
项目状态：
已结题

项目摘要

It is reported that stress is deeply concerned with the development of intestinal diseases, such as large intestine cancer, an inflammational bawel disease, and irritable colon syndrome. Therefore, we investigated the effect of the isolation stress on the gut-associated lymphoid system. ConA responses of mesenteric lymph node cells were reinforced at the acute phase of the stress, and was suppressed at the chronic phase. T/B ratio was enhanced at the acute phase, and suppressed at the chronic phase. The production of IL-4 was markedly enhanced at the chronic phase, showing the possibility of Th2 type-dominant. Thus, the mesenteric lymph node cells were notably influenced by the stress, though the spleen cells exhibited the inverse relationship. Serum cortisone levels were upregulated in acute phase, while substance P levels were upregulated in chronic phase.The influence of stress on the large intestine was analyzed in the gene discovery analysis using DNA array. Gene's upregulated sig … More nificantly compared to control were most abundant in chronic phase. Reduction of IL- 12 production and upregulation of IL- 10 and its receptor suggested that the stress changes the Th1/Th2 balance to Th2. In the sample from 2 and 30 day isolation, many genes related to hormone, neurotransmitter, and their receptors were upregulated. These results indicated that isolation stress profoundly affects the large intestine, and made it to the neuronal hypersensitivity.Next experiments were performed using chronic ulcerative colitis-induced mice by trinitrochlorobenzene (TNBS) under isolation stress load for 30 days or not. RNA was extracted from the large intestines and gene expression analysis was performed. As a result, the transcription factor & DNA-binding proteins related genes were upregulated in TNBS treated mice. The ion channels & transport proteins related genes were upregulated in mice treated with TNBS and loaded with stress. Thus, stress increases and modulates gene expression in large intestine. These results were ascertained by RT-PCR using the real-time PCR. Less

据报道，压力与肠道疾病的发展密切相关，如大肠癌，一种炎症性巴维尔病，以及结肠易激综合征。因此，我们研究了隔离应激对肠道相关淋巴系统的影响。肠系膜淋巴结细胞ConA反应在应激急性期增强，慢性期被抑制。T/B比值在急性期升高，慢性期降低。IL-4的产生在慢性期明显增强，提示可能为Th 2型优势。因此，肠系膜淋巴结细胞的显着影响的压力，虽然脾细胞表现出相反的关系。急性期血清皮质醇水平升高，慢性期血清P物质水平升高。应用基因芯片技术分析应激对大肠的影响。基因上调信号 ...更多信息与对照组相比，在慢性期最丰富。IL- 12产生的减少和IL- 10及其受体的上调表明应激改变了Th 1/Th 2平衡为Th 2。在分离2天和30天的样品中，许多与激素、神经递质及其受体相关的基因表达上调。这些结果表明，隔离应激对大肠有深刻的影响，并使大肠神经元产生超敏反应。从大肠中提取RNA并进行基因表达分析。结果表明，TNBS处理小鼠的转录因子和DNA结合蛋白相关基因表达上调。TNBS处理和应激负荷小鼠的离子通道和转运蛋白相关基因表达上调。因此，应激增加并调节大肠中的基因表达。这些结果通过使用实时PCR的RT-PCR来确定。少