Lung-Liver Axis During Pneumonia
肺炎期间的肺肝轴
基本信息
- 批准号:8288115
- 负责人:
- 金额:$ 24.65万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-09-01 至 2014-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcute Lung InjuryAcute-Phase ProteinsAcute-Phase ReactionAddressAlveolarAmyloidApoptoticBacterial PneumoniaBindingBiologicalBiological MarkersBiological ProcessBloodC-reactive proteinCell LineCellsCessation of lifeChemotaxisComplementCytokine SignalingDataDisease ProgressionEdemaEnvironmentEscherichiaEscherichia coliGene DeletionGene ExpressionGenesGoalsHepaticHepatocyteHost DefenseImmune responseIn VitroIndividualInfectionInfection preventionInflammationInflammatoryInflammatory ResponseInterleukin-1Interleukin-6LaboratoriesLiverLower respiratory tract structureLungMeasuresMediatingMediator of activation proteinMentorsMessenger RNAMusNF-kappa BNatural ImmunityNeutrophil InfiltrationOutcomePatientsPhagocytosisPhasePlasmaPlasma ProteinsPneumoniaPreventionProtein BindingProteinsPublic Health SchoolsRecombinant CytokinesResearchRoleSTAT3 geneSerumSerum amyloid A proteinSignal PathwaySignal TransductionSmall Interfering RNAStat3 proteinStreptococcus pneumoniaeSystemTestingTranscriptional RegulationTumor Necrosis Factor ReceptorTumor Necrosis Factor-alphabaseburden of illnesscareercareer developmentchromatin immunoprecipitationcytokinein vivoinnovationknock-downleukocyte activationlipopolysaccharide-binding proteinloss of functionlung injurymicrobialneutralizing antibodynew therapeutic targetnovel strategiesprogramspromoterprotein expressionresponsetooltranscription factor
项目摘要
DESCRIPTION (provided by applicant):
Lung infections account for a tremendous burden of disease worldwide, representing the most frequent cause of infection-related deaths and a common cause of acute lung injury. The long term goal of both the candidate and his laboratory is to elucidate intra- and extra-pulmonary signaling pathways required for host defense and the prevention of lung injury. The candidate has focused on pulmonary host defense since initiating his research career, and has through his accomplishments demonstrated a strong commitment to academic research. He is conducting research in a successful environment, Harvard School of Public Health, which is wholly suited to maximize his career development during the mentored phase and, ultimately, his transition toward independence. Prevention of lung infections requires a local inflammatory response that is facilitated by early response cytokines (TNF-a and IL-1) and IL-6. These cytokines signal in large part through NF-kappaB RelA and STATS, respectively. Local pulmonary immune responses occur in tandem with a systemic acute phase response (APR). Although the APR has long been recognized as a useful biomarker of disease progression during pneumonia, mechanisms mediating the APR and the collective impact of acute phase proteins (APPs) on inflammation and host defense during pneumonia are unknown. The central hypothesis of the proposed research plan is that during pneumonia, acute phase responses are induced by STATS and RelA activation in the liver and are necessary for host defense in the lung. To address this, the candidate aims to test the specific hypotheses that, during pneumonia, (1) the activation of STATS and RelA and the expression of APPs in hepatocytes require TNF-a, IL-1, and IL-6, (2) STATS and RelA in hepatocytes are required for APP expression, and (3) STATS and RelA in hepatocytes contribute to inflammation and host defense in the lungs. These studies will employ innovative approaches, including the use of mice with hepatocyte-targeted (Cre-LoxP-mediated) gene deletions of RelA, STATS or both RelA and STATS. Preliminary data support the central hypothesis and the feasibility of the proposed experimental approaches. Completion of these studies will demonstrate whether mechanisms regulating APP expression in the liver may be novel therapeutic targets for patients with pneumonia or other severe infections.
描述(由申请人提供):
肺部感染造成了全世界疾病的巨大负担,代表了与感染有关的死亡原因最常见的原因和急性肺损伤的常见原因。候选人和他的实验室的长期目标是阐明宿主防御所需的肺内和肺外信号通路和预防肺部损伤。自从启动研究生涯以来,候选人一直专注于肺部宿主防御,并通过他的成就表现出对学术研究的坚定承诺。他正在成功的环境中进行研究,哈佛公共卫生学院完全适合在指导阶段最大化他的职业发展,最终是他向独立的过渡。预防肺部感染需要局部炎症反应,这是由早期反应细胞因子(TNF-A和IL-1)和IL-6促进的。这些细胞因子在很大程度上通过NF-kappab Rela和Stats发出信号。局部肺免疫反应与全身性急性相反应(APR)同时发生。尽管长期以来,APR一直被认为是肺炎期间疾病进展的有用生物标志物,但介导APR和急性期蛋白(APP)对肺炎期间炎症和宿主防御的集体影响的机制尚不清楚。拟议的研究计划的核心假设是,在肺炎期间,急性期反应是由肝脏中的统计数据和RELA激活诱导的,对于肺中的宿主防御是必不可少的。为了解决这个问题,候选人旨在测试特定的假设,即在肺炎期间,(1)统计数据的激活以及肝细胞中的APP表达需要TNF-A,IL-1,IL-1和IL-6和IL-6和IL-6,(2)在App表达和(3)属性和(3)属性的hepats和Rela中的统计数据和RELA,并在Hepats和Rela中介绍Hepats和Hepats in. Hepats in. Hepat,并在HEPATS中介绍Hepat,并在HEPATS中介绍Hepate in。肺。这些研究将采用创新方法,包括将小鼠与肝细胞靶向(Cre-loxp介导的)基因缺失,RELA,统计或RELA和统计数据。初步数据支持中心假设和所提出的实验方法的可行性。这些研究的完成将证明调节肝脏中APP表达的机制是否可能是肺炎或其他严重感染患者的新型治疗靶标。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
GM-CSF: a double dose of protection during pneumonia.
GM-CSF:肺炎期间的双倍保护剂量。
- DOI:10.1152/ajplung.00022.2012
- 发表时间:2012
- 期刊:
- 影响因子:0
- 作者:Quinton,LeeJ
- 通讯作者:Quinton,LeeJ
Evaluating the NET influence of inflammation on pneumonia biology.
评估炎症对肺炎生物学的 NET 影响。
- DOI:10.1164/rccm.201209-1702ed
- 发表时间:2012
- 期刊:
- 影响因子:24.7
- 作者:Quinton,LeeJ
- 通讯作者:Quinton,LeeJ
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Lee Quinton其他文献
Lee Quinton的其他文献
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{{ truncateString('Lee Quinton', 18)}}的其他基金
LOX-1 as a protective countermeasure in response to lung infection
LOX-1 作为应对肺部感染的保护性对策
- 批准号:
10677924 - 财政年份:2023
- 资助金额:
$ 24.65万 - 项目类别:
LOX-1 as a protective countermeasure in response to lung infection
LOX-1 作为应对肺部感染的保护性对策
- 批准号:
10690260 - 财政年份:2022
- 资助金额:
$ 24.65万 - 项目类别:
Liver-derived protection during pneumonia and sepsis
肺炎和败血症期间的肝源性保护
- 批准号:
9309668 - 财政年份:2017
- 资助金额:
$ 24.65万 - 项目类别:
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