Peripheral Blood Mononuclear Cells, Exercise, and Children: Initial Mechanisms

外周血单核细胞、运动和儿童：初始机制

• 批准号: 7077883
• 负责人: DAN M COOPER
• 金额: $ 27.41万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-10 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7077883
• 关键词: adolescence (12-20); asthma; blood chemistry; cytokine; exercise; flow cytometry; gender difference; gene induction /repression; helper T lymphocyte; human puberty; human subject; immune response; leukocyte activation /transformation; leukocyte adhesion molecules; middle childhood (6-11); mixed tissue /cell culture; pathologic process; photon absorptiometry; physical fitness; polymerase chain reaction; respiratory function; whole body imaging /scanning

An alarming increase in the prevalence of childhood asthma has been observed in the past several decades and is likely the result of an interaction among poorly understood immune, environmental, and genetic factors. Exercise is a common cause of asthma exacerbation in children, and it is now known that when children exercise, even healthy children engaged in real-life activities, a robust stress/inflammatory response ensues leading to activation of immune cells and cytokines, many of which are known to be involved in the pathogenesis of asthma. A seemingly paradoxical response to exercise occurs characterized by simultaneous and vigorous pro- and anti-inflammatory activation. Whether or not the naturally occurring leukocyte stress/inflammatory response to exercise is imbalanced in pediatric asthma and contributes to exercise-induced bronchoconstriction (EIB) has not been investigated in children. The goal of this Project is to test a series of hypotheses focused on novel mechanisms that link exercise with asthma pathogenesis in children. Specifically, the aims are: To systematically measure in children and adolescents with mild persistent asthma the effects of brief bouts of exercise on leukocyte production of key cytokines and growth factors that determine TH1, TH2, and T-regulatory balance. To measure the relationship between the leukocyte response to exercise and the magnitude of EIB in children and adolescents with asthma. To determine in children and adolescents with asthma how the acute leukocyte responses to exercise are altered by fitness, habitual physical activity, body composition, and gender and maturational status. The research relies on state-of-the-art techniques to assess gene regulation in leukocytes including: microarray, RT-PCR, flow cytometry for surface and intracellular expression of key cytokines, and growth factors. A series of in-vitro cell culture experiments have been designed to determine whether leukocytes in children with asthma differ in their responses to exercise than in healthy controls; or, alternatively, whether the mechanism is found in factors within the circulation (e.g., mediators such as growth hormone, insulin-like growth factor-l and its binding proteins, interleukin-6, and heat shock proteins- mediators that are altered by exercise and are known to influence stress and immune responses. Exercise will consist of cycle ergometry with gas exchange measured breath by breath. Habitual physical activity will be measured with accelerometry, and body composition with DEXA. Lung function will be measured by spirometry before and after exercise. Lay Summary. Asthma is the major chronic disease of childhood, and exercise and play are, unfortunately, key triggers of asthma attacks. This research is designed to better understand how immune cells respond to exercise in asthma. This knowledge will help develop strategies to limit asthma attacks permitting affected children to prevent chronic lung disease and fully accrue the many health benefits of exercise during growth.

在过去的几十年中，人们观察到了童年哮喘患病率的惊人增加 并且很可能是理解的免疫，环境和遗传的相互作用的结果 因素。运动是儿童哮喘加重的常见原因，现在知道 儿童运动，甚至是从事现实生活活动的健康儿童，有力的压力/炎症反应 随之而来的导致免疫细胞和细胞因子的激活，其中许多已知与 哮喘的发病机理。对运动的看似矛盾的反应是以 同时且剧烈的促和抗炎激活。是否自然发生 白细胞应力/炎症反应对运动的运动不平衡，有助于 运动引起的支气管收缩（EIB）尚未在儿童中进行研究。这个项目的目标是 测试一系列的假设，这些假设着重于新机制，这些机制将运动与哮喘发病机理联系起来 孩子们。具体而言，目的是： 在患有轻度持续性哮喘的儿童和青少年中系统地测量短暂的影响 锻炼对白细胞产生关键细胞因子和生长因子的锻炼，这些因子决定了Th1，Th2， 和T型平衡。 测量白细胞对运动的响应与EIB幅度之间的关系 患有哮喘的儿童和青少年。 在患有哮喘的儿童和青少年中，急性白细胞对运动的反应如何 随着健身，惯常的体育锻炼，身体组成以及性别和成熟状态而改变。 该研究依靠最先进的技术来评估白细胞中的基因调节，包括： 微阵列，RT-PCR，用于表面和细胞内表达的流式细胞仪，生长 因素。已经设计了一系列体外细胞培养实验，以确定白细胞是否存在 在患有哮喘的儿童中，他们对运动的反应不同于健康对照。或者，无论是 该机制在循环中的因素中发现（例如，介质，例如生长激素，胰岛素样 生长因子-L及其结合蛋白，白介素-6和热激蛋白 - 介质会改变 运动，已知会影响压力和免疫反应。运动将包括循环测量法 用气体交换通过呼吸测量。习惯性体育锻炼将通过 加速度测定法和带有DEXA的身体组成。肺功能将通过肺活量测定法测量和 运动后。 摘要摘要。哮喘是儿童期的主要慢性疾病，不幸的是，运动和锻炼是 哮喘攻击的关键触发因素。这项研究旨在更好地了解免疫细胞如何反应 哮喘运动。这些知识将有助于制定限制允许受影响的哮喘攻击的策略 儿童预防慢性肺部疾病并充分累积运动期间运动的许多健康益处。