REGULATION OF MACROPHAGE FUNCTION BY COMPONENTS OF WOODSMOKE

木烟成分对巨噬细胞功能的调节

• 批准号: 8360466
• 负责人: CHRISTOPHER Todd MIGLIACCIO
• 金额: $ 16.81万
• 依托单位: UNIVERSITY OF MONTANA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2013-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8360466
• 关键词: Acute; Air; Aryl Hydrocarbon Receptor; Biological Assay; Biomass; Burn injury; Child; Dioxins; Environmental Health; Event; Family; Flow Cytometry; Funding; Grant; Guidelines; Health; Home environment; Human; Hydrocarbons; Immune system; In Vitro; Knockout Mice; Link; Lung; Methods; Modeling; Molecular; Molecular Biology; Mouse Strains; Mus; National Center for Research Resources; Orphan; Particulate; Pathway interactions; Principal Investigator; Regulation; Research; Research Infrastructure; Resources; Smoke; Source; Testing; Transgenic Mice; United States National Institutes of Health; Wood material; base; cigarette smoking; cooking; cost; macrophage; member; receptor binding; respiratory; transcription factor

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Wood smoke (WS) is regulated according to the EPA guidelines for air quality, which are based on urban particulate studies. Wood smoke particulates are not the same as urban particulates, but the specific health effects of WS are not defined. A variety of studies have found increases in acute respiratory illnesses (ARI) in children in homes where biomass burning (i.e. wood) is the method of cooking. Human observations point to strong links between smoke exposure and respiratory illness, but are lacking in the cellular and molecular events that are involved. By contrast, cigarette smoke (CS) research is extensive. Recent studies have linked CS with activation of the aryl hydrocarbon receptor (AhR) and its subsequent activation of the RelB member of the NF¿B family of transcription factors. AhR is an orphan receptor that binds with dioxin and dioxin-like compounds and can promote alterations in the immune system. Several groups have described multiple types of polyaromatic hydrocarbons (PAH) in WS that are the same or similar to those found in CS. We propose to assess the effects of WS components on macrophage function using a murine pulmonary model. Wood smoke-derived alterations in macrophage function will be defined by flow cytometry, molecular biology, transgenic and null mouse strains, and in vitro functional assays. We propose to test the central hypothesis that macrophage function is differentially regulated by components of wood smoke via the aryl hydrocarbon receptor and NF¿B pathway.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 根据EPA的空气质量指南，木烟（WS）受到城市特殊研究的规定。木烟组成部分与城市细节不同，但是WS的特定健康效应尚未定义。各种研究发现，在生物质燃烧（即木材）的家庭中，急性呼吸道疾病（ARI）的增加是烹饪的方法。人类的观察表明，烟雾暴露与呼吸道疾病之间存在牢固的联系，但在涉及的细胞和分子事件中缺乏联系。相比之下，香烟烟（CS）的研究是广泛的。最近的研究已将C与芳基烃受体（AHR）的激活联系起来及其随后激活NF¿B转录因子家族的RELB成员。 AHR是一种与二恶英和类似二恶英的化合物结合的孤儿受体，可以促进免疫系统的改变。几个小组描述了WS中多种类型的多芳烃（PAH），与CS中的多芳烃（PAH）相同或相似。我们建议使用鼠肺模型评估WS成分对巨噬细胞功能的影响。巨噬细胞功能的木烟来改变将由流式细胞仪，分子生物学，转基因和无效小鼠菌株以及体外功能分析来定义。我们建议检验中心假设，即巨噬细胞功能通过芳基烃受体和NF途径的木烟的成分差异地调节。