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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以出现在其他 CRISP 条目中 列出的机构是。 对于中心来说，它不一定是研究者的机构。 越来越多的证据表明，T 细胞在抗原刺激后调节动脉粥样硬化中的炎症，幼稚 T 细胞分化为辅助性 T 细胞 1 (Th1) 或辅助性 T 细胞 2 (Th2)，这些细胞在外周消失，进入动脉病变并进入动脉。 Th1 细胞构成人类动脉粥样硬化病变中的大部分 T 细胞，其分泌的细胞因子很大程度上是其谱系特异的，并分泌维持持续存在的促炎细胞因子。 Th1 细胞因子被 Th2 细胞特异性细胞因子下调，而 Th2 细胞也可能存在于动脉粥样硬化病变中，但数量要少得多 1。受外周 Th1 与 Th2 细胞比例及其谱系特异性效应的影响。 据我们所知，尚无已发表的报告描述健康成年狒狒外周血中测量的一组全面的 Th1 和 Th2 谱系特异性细胞因子水平的正常变异或基因附加效应的估计。在这里，我们建议通过体内测量 10 种有助于促炎 Th1 和抗炎 Th2 作用的细胞因子来表征 Th1 和 Th2 谱系特异性细胞因子水平的正常变化。 384只健康狒狒。 具体来说，我们将： 1) 描述 IFN 水平正常基线变异的分布、血清中的淋巴毒素 (TNF¿)、IL-12p40、IL-12p70、IL-15 和 IL-18（Th1 细胞因子）以及 IL-4、IL-5、IL-10 和 IL-13（Th2 细胞因子）来自 384 只健康狒狒，未接受过病毒或饮食挑战等实验挑战； 2) 通过估计每种检测到的细胞因子的遗传力或可归因于加性遗传效应的表型变异比例，展示和评估加性遗传变异的影响； 3) 测量所有检测到的细胞因子的多效性或共享遗传效应的程度。