REGULATION OF MACROPHAGE FUNCTION BY COMPONENTS OF WOODSMOKE

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 木材烟雾(WS)是根据EPA空气质量指南进行监管的，该指南基于城市颗粒物研究。木材烟雾颗粒物与城市颗粒物不同，但WS对健康的具体影响并未定义。各种研究发现，在以生物质燃烧(即木头)为烹饪方法的家庭中，儿童急性呼吸道疾病(ARI)的发病率会增加。人类的观察表明，吸烟与呼吸系统疾病之间存在密切联系，但在相关的细胞和分子事件中缺乏这种联系。相比之下，香烟烟雾(CS)的研究是广泛的。最近的研究将CS与芳烃受体(AhR)的激活以及随后的转录因子家族转录因子RelB成员的激活联系在一起。AHR是一种孤儿受体，与二恶英和二恶英类化合物结合，可以促进免疫系统的变化。几个组已经描述了WS中与CS中发现的相同或相似的多种类型的多芳烃(PAH)。我们建议使用小鼠肺模型来评估WS组分对巨噬细胞功能的影响。木材烟雾引起的巨噬细胞功能的改变将通过流式细胞术、分子生物学、转基因和零基因小鼠品系以及体外功能分析来确定。我们建议检验中心假设，巨噬细胞的功能是通过芳烃受体和核因子B途径受到木材烟雾成分的不同调节。

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. 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.