Arsenic and Innate Immunity in Human Lung
Arsenic and Innate Immunity in Human Lung
批准号:
8881879
负责人:
Bruce A. Stanton
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
项目状态:
已结题
起止时间:
2014-07-01 至 2015-03-31
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
中文摘要
点击翻译按钮获取中文摘要
英文摘要
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.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Let-7b in Extracellular Vesicles Secreted by Bronchial Epithelial Cells Increases the Antibiotic Sensitivity of Pseudomonas
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批准号:10319005
-
项目类别:
-
资助金额:$53.94万
-
财政年份:2020
-
负责人:Bruce A. Stanton
-
依托单位:
Let-7b in Extracellular Vesicles Secreted by Bronchial Epithelial Cells Increases the Antibiotic Sensitivity of Pseudomonas
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批准号:10525239
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项目类别:
-
资助金额:$53.94万
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财政年份:2020
-
负责人:Bruce A. Stanton
-
依托单位:
Retrieval, Reprocessing, Normalization and Sharing of Gene Expression and Lung Microbiome Data Sets to Facilitate AI/ML Analysis Studies of Bacterial Lung Infections
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批准号:10594180
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项目类别:
-
资助金额:$26.24万
-
财政年份:2020
-
负责人:Bruce A. Stanton
-
依托单位:
Gastrointestinal Biology Core
-
批准号:10001761
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项目类别:
-
资助金额:$21.97万
-
财政年份:2018
-
负责人:Bruce A. Stanton
-
依托单位:
CF Bioinformatics and Biostatistics Core
-
批准号:10001763
-
项目类别:
-
资助金额:$25.11万
-
财政年份:2018
-
负责人:Bruce A. Stanton
-
依托单位:
Gastrointestinal Biology Core
-
批准号:10686312
-
项目类别:
-
资助金额:$21.97万
-
财政年份:2018
-
负责人:Bruce A. Stanton
-
依托单位:
CF Bioinformatics and Biostatistics Core
-
批准号:10686327
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项目类别:
-
资助金额:$25.11万
-
财政年份:2018
-
负责人:Bruce A. Stanton
-
依托单位:
Gastrointestinal Biology Core
-
批准号:10241580
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项目类别:
-
资助金额:$21.97万
-
财政年份:2018
-
负责人:Bruce A. Stanton
-
依托单位:
CF Bioinformatics and Biostatistics Core
-
批准号:10241582
-
项目类别:
-
资助金额:$25.11万
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财政年份:2018
-
负责人:Bruce A. Stanton
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依托单位:
Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research
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批准号:9115188
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项目类别:
-
资助金额:$118.59万
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财政年份:2013
-
负责人:Bruce A. Stanton
-
依托单位:
Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research
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批准号:8727639
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项目类别:
-
资助金额:$120.07万
-
财政年份:2013
-
负责人:Bruce A. Stanton
-
依托单位:
Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research
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批准号:8514218
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项目类别:
-
资助金额:$120.84万
-
财政年份:2013
-
负责人:Bruce A. Stanton
-
依托单位:
Dartmouth Lung Biology Center for Molecular, Cellular and Translational Research
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批准号:8899599
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项目类别:
-
资助金额:$119.32万
-
财政年份:2013
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: CELL BIOLOGY AND IMAGING CORE
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批准号:8359700
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项目类别:
-
资助金额:$22.36万
-
财政年份:2011
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: FACULTY DEVELOPMENT CORE
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批准号:8359701
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项目类别:
-
资助金额:$32.31万
-
财政年份:2011
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: ADMINISTRATIVE CORE
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批准号:8359699
-
项目类别:
-
资助金额:$31.17万
-
财政年份:2011
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: ADMINISTRATIVE CORE
-
批准号:8167467
-
项目类别:
-
资助金额:$31.7万
-
财政年份:2010
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: FACULTY DEVELOPMENT CORE
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批准号:8167469
-
项目类别:
-
资助金额:$19.61万
-
财政年份:2010
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: CELL BIOLOGY AND IMAGING FACILITY CORE
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批准号:8167468
-
项目类别:
-
资助金额:$33.75万
-
财政年份:2010
-
负责人:Bruce A. Stanton
-
依托单位:
COBRE: ADMINISTRATIVE CORE
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批准号:7960366
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项目类别:
-
资助金额:$31.97万
-
财政年份:2009
-
负责人:Bruce A. Stanton
-
依托单位:
海外基金