CYTOKINES ASSOCIATED WITH T-HELPER CELL SUBSET EFFECTS ON ATHEROSCLEROSIS

与 T 辅助细胞亚群对动脉粥样硬化影响相关的细胞因子

• 批准号: 7716107
• 负责人: Amanda Vinson
• 金额: $ 0.1万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7716107
• 关键词: Adult; Anti-Inflammatory Agents; Anti-inflammatory; Antigens; Arterial Fatty Streak; Atherosclerosis; Cardiovascular Diseases; Cells; Computer Retrieval of Information on Scientific Projects Database; Funding; Genes; Genetic; Genetic Models; Genetic Variation; Grant; Helper-Inducer T-Lymphocyte; Heritability; Human; Human Genetics; Inflammation; Inflammatory; Institution; Interleukin-10; Interleukin-13; Interleukin-15; Interleukin-18; Interleukin-4; Interleukin-5; Knowledge; Measurement; Measures; Normal Statistical Distribution; Papio; Predisposition; Publishing; Reporting; Research; Research Personnel; Resources; Risk Factors; Serum; Source; T-Lymphocyte; Tumor Necrosis Factor-Beta; United States National Institutes of Health; Variant; Viral; arterial lesion; cytokine; in vivo; interleukin-12 subunit p40; peripheral blood; pleiotropism

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Increasing evidence indicates that T-cells modulate inflammation in atherosclerosis. Following antigen stimulation, naive T-cells differentiate into either T-helper 1 (Th1) or T-helper 2 (Th2) cells, which circulate in the periphery, enter arterial lesions and secrete cytokines that are largely specific to their lineage. Th1 cells constitute most of the T-cells in human atherosclerotic lesions1, and secrete pro-inflammatory cytokines that sustain ongoing inflammation in the lesion2. Th1 cytokines are down-regulated by cytokines specific to Th2 cells3, which may also be present in atherosclerotic lesions but in far fewer numbers1. Thus, generalized inflammation, susceptibility to atherosclerosis, and subsequent cardiovascular disease (CVD) may be influenced by the ratio in the periphery of Th1 to Th2 cells and their lineage-specific effects. To the best of our knowledge, there are no published reports describing normal variation for, or estimates of the additive effects of genes on, a comprehensive set of Th1 and Th2 lineage-specific cytokine levels measured in peripheral blood for the healthy adult baboon, a valuable model for the genetics of human atherosclerosis risk factors. Here, we propose to characterize normal variation in Th1 and Th2 lineage-specific cytokine levels by measurement in vivo of 10 cytokines that contribute to pro-inflammatory Th1 and anti-inflammatory Th2 effects in 384 healthy baboons. Specifically, we will: 1) Characterize the distribution of normal baseline variation in levels of IFN¿, lymphotoxin (TNF¿), IL-12p40, IL-12p70, IL-15, and IL-18 (Th1 cytokines) and IL-4, IL-5, IL-10, and IL-13 (Th2 cytokines) in serum from 384 healthy baboons that have not been exposed to experimental challenge, such as viral or dietary challenge; 2) Demonstrate and assess the influence of additive genetic variation by estimating heritability, or the proportion of phenotypic variance attributable to additive genetic effects, for each detected cytokine; 3) Measure the extent of pleiotropy, or shared genetic effects, among all detected cytokines.

该副本是使用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这是调查员的机构。 越来越多的证据表明，T细胞在动脉粥样硬化中调节炎症。抗原刺激后，幼稚的T细胞分化为T-Helper 1（Th1）或T辅助2（Th2）细胞，这些细胞在周围圆圈中圆满，进入伪影，并在很大程度上特异性地特定于其谱系。 Th1细胞构成人动脉粥样硬化病变中的大多数T细胞，以及秘密的促炎细胞因子，可维持病变中持续炎症2。 Th1细胞因子被特异性的Th2细胞3的细胞因子下调，Th2细胞3也可能存在于动脉粥样硬化病变中，但数量较少。因此，广义感染，对动脉粥样硬化的易感性以及随后的心血管疾病（CVD）可能受到TH1与Th2细胞外围的比率及其谱系特异性作用的影响。 据我们所知，尚无公开的报告描述基因对基因添加作用的正常变化或估计，是健康成人狒狒外周血中测量的一组TH1和TH2谱系特异性细胞因子水平，这是人类动脉粥样硬化风险因素的遗传学的有价值模型。在这里，我们建议通过在体内测量10种细胞因子的测量，以表征Th1和Th2谱系特异性细胞因子水平的正常变异，这些细胞因子有助于促炎性TH1和384个健康狒狒的抗炎Th2效应。 具体来说，我们将： 1）表征IFN¿，淋巴毒素（TNF¿），IL-12P40，IL-12P70，IL-15和IL-15和IL-18（TH1细胞因子）和IL-4，IL-4，IL-5，IL-5，IL-10，IL-10，IL-10和IL-13（IL-13（IL-13）（IL-13（IL-13）（IL-13）（Th2 Cytokines in s serum serums in s serum serums in s s serum serums in s s s s serum s s s s s s s serums）non 384，serum notiention not 384，表征了3844444444.作为病毒或饮食挑战； 2）通过估计遗传力或对每个检测到的细胞因子归因于加性遗传效应的表型方差的比例来证明和评估添加遗传变异的影响； 3）在所有检测到的细胞因子中测量多效性或共享遗传作用的程度。