Endotoxin, allergens and pollutants in asthma

哮喘中的内毒素、过敏原和污染物

• 批准号: 7488818
• 负责人: Daniel G. Remick
• 金额: $ 33.75万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-15 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7488818
• 关键词: Acute; Affinity Chromatography; Air; Air Pollutants; Air Pollution; Allergens; Animals; Asthma; Attention; Bacteria; Cells; Child; Chronic; Crohn' s disease; Data; Developed Countries; Developing Countries; Development; Dictyoptera; Disease; Documentation; Endotoxins; Environmental Risk Factor; Excision; Exposure to; Genetic; Histology; Home environment; House Dust; Immune response; Incidence; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Language; Lung; Measures; Mediator of activation protein; Michigan; Modality; Modeling; Mus; Outcome; Particulate; Pathogenesis; Pathway interactions; Patients; Pharmaceutical Preparations; Pneumonia; Population; Probability; Process; Pulmonary function tests; Range; Research Personnel; Resources; Rheumatoid Arthritis; Role; Symptoms; TLR4 gene; Testing; Transcriptional Activation; Triad Acrylic Resin; Tumor Necrosis Factor-alpha; Tumor Necrosis Factors; United States; Universities; Up-Regulation; Work; base; cockroach allergen; human TNF protein; insight; novel; particle; pollutant; prevent; programs; research study; response; success

DESCRIPTION (provided by applicant): It is clear that the disease process known as asthma is on the increase in the United States and other developed countries. This increase in the incidence of asthma is not due to changes in the genetic makeup of the population, but rather a combination of environmental factors. Some of the triggers for asthma have been delineated, as well as the actual molecules that drive the inflammatory response. However, the full spectrum of the inflammatory mediators responsible for the initiation and propagation of asthma have yet to be fully defined. We have established a novel model of murine asthma-like pulmonary inflammation based on house dust from the homes of children with asthma. In this application we will build on this novel model to provide closer documentation of the initiators and propagators of the asthma like response. We will pay particular attention to the mechanisms of how these initiators trigger an asthmatic response. Perhaps of greater importance, we will define the inflammatory molecules upregulated by the environmental triggers with particular emphasis on tumor necrosis factor (TNF). The application will focus on the triumvirate of endotoxin, allergens, and outdoor pollutants both singly and in combination. The first specific aim will look at the role of endotoxin in triggering the asthmatic response. This specific aim will use a combination of removing endotoxin from the house dust in addition to examining endotoxin tolerant animals. Using more than one approach increases the probability of success, as well as enhances the rigor of the observations. In the second specific aim, we will remove the allergen from the house dust extract. In the third specific aim we will determine the potential for concentrated air particles, which represent outdoor pollutants, to exacerbate the asthmatic response. Additionally, we will determine whether exposure to the concentrated air particles will prime an animal to develop an asthmatic response. For each of these specific aims we will not only determine if inflammation is present, but also define the range of inflammatory mediators. In our last specific aim we will integrate the data from the previous work to decrease the asthmatic response by blocking TNF by multiple modalities. The results from these studies will define the participation of endotoxin, allergens and outdoor pollutants in the pathogenesis of asthma and determine the role of TNF in causing the inflammation. Lay language: This application will examine how house dust causes asthma. It will specifically examine how 2 different components found in the house dust, cockroaches and bacteria, interact with outdoor air pollution to result in pulmonary inflammation. We will also investigate if a new drug approved for the treatment of rheumatoid arthritis will also help prevent asthma.

描述（由申请人提供）：很明显，称为哮喘的疾病过程正在美国和其他发达国家增加。哮喘发病率的增加不是由于人口基因组成的变化，而是环境因素的结合。一些哮喘的触发因素已被描述，以及驱动炎症反应的实际分子。但是，负责哮喘起始和传播的炎症介体的全部范围尚未得到充分定义。我们已经建立了一种基于哮喘儿童家中尘埃的鼠类哮喘状肺部炎症的新型模型。在此应用程序中，我们将基于这个新颖的模型，以提供哮喘反应的发起人和传播者的更紧密文档。我们将特别注意这些发起人如何引发哮喘反应的机制。也许更重要的是，我们将定义由环境触发因素上调的炎症分子，并特别着重于肿瘤坏死因子（TNF）。该应用程序将重点介绍内毒素，过敏原和室外污染物的trium，既可以单独又结合使用。第一个具体目的将考虑内毒素在触发哮喘反应中的作用。除了检查内毒素耐受性动物外，该特定目标还将结合从房屋灰尘中去除内毒素。使用多种方法增加了成功的可能性，并增强了观察结果的严格性。在第二个特定目的中，我们将从房屋粉尘提取物中取出过敏原。在第三个特定目的中，我们将确定代表室外污染物的浓缩空气颗粒的潜力，以加剧哮喘反应。此外，我们将确定暴露于浓缩空气颗粒是否会产生动物以产生哮喘反应。对于这些特定目的，我们不仅将确定是否存在炎症，而且还定义了炎症介质的范围。在我们的最后一个特定目标中，我们将通过以上工作的方式整合数据，以通过多种模式阻止TNF来减少哮喘响应。这些研究的结果将定义内毒素，过敏原和室外污染物在哮喘发病机理中的参与，并确定TNF在引起炎症中的作用。外行语言：此应用程序将检查房屋灰尘如何导致哮喘。它将专门研究在房屋灰尘，蟑螂和细菌中发现的2种不同的成分如何与室外空气污染相互作用，从而导致肺部炎症。我们还将调查是否批准一种用于治疗类风湿关节炎的新药也将有助于预防哮喘。