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.

在过去的几十年里，儿童哮喘的患病率出现了令人震惊的增长 这很可能是人们对免疫、环境和遗传之间相互作用知之甚少的结果 因素。运动是儿童哮喘恶化的常见原因，现在已知，当 儿童锻炼，甚至健康的儿童参与现实生活中的活动，都会产生强烈的压力/炎症反应 随后导致免疫细胞和细胞因子的激活，其中许多已知参与 哮喘的发病机制。对运动的看似矛盾的反应的特征是 同时且强烈的促炎和抗炎激活。是否自然发生 小儿哮喘中白细胞对运动的应激/炎症反应不平衡，导致 运动引起的支气管收缩（EIB）尚未在儿童中进行过研究。该项目的目标是 测试一系列假设，重点关注将运动与哮喘发病机制联系起来的新机制 孩子们。具体来说，目标是： 系统地测量短期治疗对患有轻度持续性哮喘的儿童和青少年的影响 运动对白细胞产生关键细胞因子和生长因子的影响，这些细胞因子和生长因子决定 TH1、TH2、 和T-监管平衡。 测量白细胞对运动的反应与 EIB 大小之间的关系 患有哮喘的儿童和青少年。 确定患有哮喘的儿童和青少年的急性白细胞对运动的反应如何 因健康状况、习惯性身体活动、身体成分、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的基因调控，包括： 微阵列、RT-PCR、流式细胞术检测关键细胞因子的表面和细胞内表达以及生长 因素。设计了一系列体外细胞培养实验来确定白细胞是否 哮喘儿童对运动的反应与健康对照组不同；或者，或者，是否 该机制存在于循环系统内的因素中（例如生长激素、胰岛素样介质等介质） 生长因子-1 及其结合蛋白、白细胞介素-6 和热休克蛋白 - 介质，可通过以下方式改变 锻炼会影响压力和免疫反应。锻炼将包括自行车测功 通过每次呼吸测量气体交换。习惯性体力活动将通过以下方式进行测量 使用 DEXA 进行加速度测量和身体成分分析。之前和之后将通过肺量计测量肺功能 运动后。 平铺总结。哮喘是儿童时期的主要慢性疾病，不幸的是，锻炼和玩耍 哮喘发作的关键诱因。这项研究旨在更好地了解免疫细胞如何应对 运动治疗哮喘。这些知识将有助于制定限制哮喘发作的策略，让受影响的人 儿童预防慢性肺部疾病，并在成长过程中充分获得运动的诸多健康益处。