Arsenic and Innate Immunity in Human Lung
砷与人肺的先天免疫
基本信息
- 批准号:8881879
- 负责人:
- 金额:$ 0.12万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-07-01 至 2015-03-31
- 项目状态:已结题
- 来源:
- 关键词:AcidsAcuteAddressAdverse effectsAffectAmericanAnimal ModelAnimalsArsenicArsenitesBacterial InfectionsBiochemicalBioinformaticsBiologicalBloodBronchiectasisCardiovascular DiseasesCause of DeathChronicChronic Obstructive Airway DiseaseCommunitiesCystic FibrosisCytokine GeneDevelopmentDiabetes MellitusDoseDown-RegulationEnvironmental ExposureEpidemiologic StudiesEpithelial CellsExposure toFoodFood SafetyFunctional RNAGene ExpressionGenesGoalsHealthHumanIL8 geneImmuneImmune responseImmune systemInfectionInflammatory ResponseInterleukin-6KnowledgeLaboratoriesLeadLungLung diseasesMalignant NeoplasmsMeasuresMercuryMicroRNAsModelingMolecularMorbidity - disease rateNatural ImmunityPathway interactionsPatientsPlayPneumoniaPopulationPost-Translational RegulationProductionPseudomonasPseudomonas aeruginosaRelative (related person)Respiratory Tract InfectionsRespiratory physiologyRiceRiskRoleSourceTNF geneTestingVirus Diseasesabstractingbasecytokinedrinking waterearly childhoodearly life exposureenvironmental chemicalin uteroinhibitor/antagonistinsightmRNA Expressionmacrophagemonomethylarsonic acidmortalitynovelpathogenprotein expressionreproductiveresponsetoolyoung adult
项目摘要
Project 3: Abstract
Arsenic (As) is the number one environmental chemical of concern with regard to human health in the US.
Epidemiological studies have shown that exposure to As increases lung disease, including pneumonia, and
chronic obstructive pulmonary disease. In studies on experimental animals low levels of As inhibit the ability of
the innate immune system to eliminate respiratory infections, and down regulate the expression of innate
immune genes, but the molecular mechanisms whereby As inhibits the innate immune system is unknown.
Moreover, the effects of inorganic versus organic As on the innate immune system is unknown. Accordingly,
the goal of this application is to test the hypothesis that inorganic and organic forms have differential, dose
dependent effects on the Pseudomonas aeruginosa (Pa) infections in the lung by adversely affecting the innate
immune response. This will be investigated in two specific aims. Specific Aim #1 will test the hypothesis that
arsenite, monomethylarsonic acid (MMA) and dimetheylarsinic acid (DMA) have differential, dose dependent
effects on the secretion of proinflammatory cytokines by human bronchial epithelial (HBE) cells and
macrophages in response to Pa. Studies will be conducted to examine the effects of arsenite, MMA and DMA,
at levels relevant to the US population, on cytokine production by HBE cells and macrophages exposed to Pa.
Specific Aim #2 will test the hypothesis that arsenite, MMA and DMA have differential, dose dependent effects
on the expression of proinflammatory cytokine genes by HBE cells and macrophages in response to Pa by
selectively regulating microRNA (miRNA) expression. Using advanced bioinformatic and molecular biological
approaches, studies will be conducted to elucidate how miRNAs regulated by As modulate the inflammatory
response to Pa. These studies will provide novel information regarding the dose and species dependent effects
of arsenite, MMA and DMA, at levels relevant to the US population, on the immune response to Ps, a pathogen
that causes significant morbidity and mortality in the US, as well as provide novel insight into the molecular
mechanism(s) whereby As modulates the innate immune response of the human lung to Pa.
项目3:摘要
在美国,砷(As)是与人类健康有关的头号环境化学品。
流行病学研究表明,接触砷会增加肺部疾病,包括肺炎,以及
慢性阻塞性肺病。在对实验动物的研究中,低水平的砷抑制了
先天免疫系统能消除呼吸道感染,并下调先天基因的表达
免疫基因,但AS抑制先天性免疫系统的分子机制尚不清楚。
此外,无机砷与有机砷对先天免疫系统的影响尚不清楚。因此,
这一应用的目标是检验无机和有机形态具有不同剂量的假设。
肺部铜绿假单胞菌感染对先天感染的依赖作用
免疫反应。这将在两个具体目标下进行调查。第一个具体目标将检验这一假设
亚砷酸盐、一甲基砷酸(MMA)和二甲基砷酸(DMA)具有不同的剂量依赖性
对人支气管上皮细胞分泌促炎细胞因子的影响
巨噬细胞对PA的反应。将进行研究,以检查亚砷酸盐、MMA和DMA的影响,
在与美国人口相关的水平上,对暴露于PA的HBE细胞和巨噬细胞产生细胞因子的影响。
特殊目标#2将检验亚砷酸盐、甲基丙烯酸甲酯和二甲基亚硝胺具有不同的剂量依赖效应的假设
PA对HBE细胞和巨噬细胞促炎细胞因子基因表达的影响
选择性地调节microRNA(MiRNA)的表达。利用先进的生物信息学和分子生物学
方法,将进行研究,以阐明AS调节的miRNAs如何调节炎症
对爸爸的回应。这些研究将提供有关剂量和物种依赖效应的新信息。
亚砷酸盐、MMA和DMA在与美国人口相关的水平上对病原体Ps的免疫反应
这在美国导致了显著的发病率和死亡率,并为分子生物学提供了新的见解
AS调节人肺对PA的先天免疫反应的机制(S)。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Bruce A. Stanton其他文献
New insights into cystic fibrosis: molecular switches that regulate CFTR
囊性纤维化的新见解:调节 CFTR 的分子开关
- DOI:
10.1038/nrm1949 - 发表时间:
2006-06-01 - 期刊:
- 影响因子:90.200
- 作者:
William B. Guggino;Bruce A. Stanton - 通讯作者:
Bruce A. Stanton
Characterization of apical and basolateral membrane conductances of rat inner medullary collecting duct.
大鼠内髓集合管顶膜和基底外侧膜电导的表征。
- DOI:
- 发表时间:
1989 - 期刊:
- 影响因子:0
- 作者:
Bruce A. Stanton - 通讯作者:
Bruce A. Stanton
Lung-kidney axis in cystic fibrosis: Early urinary markers of kidney injury correlate with neutrophil activation and worse lung function
囊性纤维化中的肺-肾轴:肾脏损伤的早期尿液标志物与中性粒细胞活化和更差的肺功能相关
- DOI:
10.1016/j.jcf.2024.12.007 - 发表时间:
2025-05-01 - 期刊:
- 影响因子:6.000
- 作者:
Grace M. Rosner;Himanshu B. Goswami;Katherine Sessions;Lindsay K. Mendyka;Brenna Kerin;Irma Vlasac;Diane Mellinger;Lorraine Gwilt;Thomas H. Hampton;Martha Graber;Alix Ashare;William T. Harris;Brock Christensen;Bruce A. Stanton;Agnieszka Swiatecka-Urban;Sladjana Skopelja-Gardner - 通讯作者:
Sladjana Skopelja-Gardner
Bruce A. Stanton的其他文献
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{{ truncateString('Bruce A. Stanton', 18)}}的其他基金
Let-7b in Extracellular Vesicles Secreted by Bronchial Epithelial Cells Increases the Antibiotic Sensitivity of Pseudomonas
支气管上皮细胞分泌的胞外囊泡中的 Let-7b 增加假单胞菌的抗生素敏感性
- 批准号:
10319005 - 财政年份:2020
- 资助金额:
$ 0.12万 - 项目类别:
Let-7b in Extracellular Vesicles Secreted by Bronchial Epithelial Cells Increases the Antibiotic Sensitivity of Pseudomonas
支气管上皮细胞分泌的胞外囊泡中的 Let-7b 增加假单胞菌的抗生素敏感性
- 批准号:
10525239 - 财政年份:2020
- 资助金额:
$ 0.12万 - 项目类别:
Retrieval, Reprocessing, Normalization and Sharing of Gene Expression and Lung Microbiome Data Sets to Facilitate AI/ML Analysis Studies of Bacterial Lung Infections
基因表达和肺部微生物组数据集的检索、再处理、标准化和共享,以促进细菌肺部感染的 AI/ML 分析研究
- 批准号:
10594180 - 财政年份:2020
- 资助金额:
$ 0.12万 - 项目类别:
Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research
达特茅斯肺生物学分子、细胞和转化研究中心
- 批准号:
9115188 - 财政年份:2013
- 资助金额:
$ 0.12万 - 项目类别:
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