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.

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 越来越多的证据表明，T细胞调节动脉粥样硬化中的炎症。抗原刺激后，初始T细胞分化为辅助性T细胞1（Th 1）或辅助性T细胞2（Th 2），其在外周循环，进入动脉病变并分泌对其谱系具有很大特异性的细胞因子。 Th 1细胞构成人类动脉粥样硬化病变中的大部分T细胞1，并分泌维持病变中持续炎症的促炎细胞因子2。 Th 1细胞因子被Th 2细胞特异性细胞因子下调3，Th 2细胞也可能存在于动脉粥样硬化病变中，但数量少得多1。 因此，全身性炎症、动脉粥样硬化易感性和随后的心血管疾病（CVD）可能受到外周Th 1/Th 2细胞比例及其谱系特异性效应的影响。 据我们所知，目前还没有发表的报告描述正常的变化，或估计基因的加性效应，一套全面的Th 1和Th 2谱系特异性细胞因子水平测量外周血中的健康成年狒狒，人类动脉粥样硬化危险因素的遗传学的一个有价值的模型。 在这里，我们建议在384只健康狒狒的促炎性Th 1和抗炎性Th 2效应的10种细胞因子的体内测量来表征Th 1和Th 2谱系特异性细胞因子水平的正常变化。 具体而言，我们将： 第一章 表征384只未暴露于实验性攻毒（如病毒或饮食攻毒）的健康狒狒血清中IFN？、光毒素（TNF？）、IL-12 p40、IL-12 p70、IL-15和IL-18（Th 1细胞因子）以及IL-4、IL-5、IL-10和IL-13（Th 2细胞因子）水平的正常基线变化分布; （二） 通过估计每种检测到的细胞因子的遗传力或归因于加性遗传效应的表型方差的比例，证明和评估加性遗传变异的影响; 第三章 在所有检测到的细胞因子中，测量多效性或共享遗传效应的程度。