Role of neutrophil extracellular traps (NETs) in Inflammatory bowel disease
中性粒细胞胞外陷阱(NET)在炎症性肠病中的作用
基本信息
- 批准号:10608277
- 负责人:
- 金额:$ 43.69万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-15 至 2027-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAddressAdhesionsAffectAggravated ColitisAmericanArginineArginine deiminaseAwarenessBiomassCXCR4 geneCellsChargeChronicCitrullineColitisCrohn&aposs diseaseCytoplasmic GranulesDNADataDeoxyribonuclease IDiseaseElastasesEnzymesExcisionFunctional disorderGastrointestinal tract structureGenerationsGeneticGoalsHistonesHomeostasisHumanImmuneImmune responseInflammationInflammatoryInflammatory Bowel DiseasesInflammatory ResponseIntestinal DiseasesIntestinesKnowledgeLCN2 geneLiteratureMediatingMediatorMicrobeModelingMolecularMucositisMucous MembraneMusNeutrophiliaPathologicPathologyPathway interactionsPeptide HydrolasesPeroxidasesPhagocytesPredispositionProteinsReactive Oxygen SpeciesRecoveryRegulationRelapseReportingResearchRoleSodium Dextran SulfateStructureTherapeuticUlcerative ColitisUnited Statesadverse outcomeantagonistantimicrobialbactericidecell typeclinically relevantcombatdisease diagnosisextracellularfirst respondergastrointestinalgut bacteriagut healthgut inflammationhost microbiotain vivo Modelinterleukin-10 receptormicrobialmouse modelneutrophilopportunistic pathogenpancreatic elastase IIpharmacologicpreventrecruitresponsetherapeutic targettranslational applicationstranslational approachwound healing
项目摘要
Project Summary
In 2020, approximately 1.6 million Americans were confirmed to have inflammatory bowel disease (IBD)
and it is expected that as many as 70,000 new cases of IBD are diagnosed in the United States each year. IBD
comprises of chronic, relapsing inflammatory disorders affecting the gastrointestinal (GI) tract, such as Crohn’s
Disease and Ulcerative Colitis. Among various immune cells that participate in IBD, neutrophils are not only the
first responder cell-type to inflammation, but also involved in limiting inflammation and facilitating wound repair.
Of note, there is a dearth of literature on the mucoprotective role of the enzyme peptidyl arginine deiminase-4
(PAD4), whose predominant function is to facilitate the generation of citrullinated histone 3 (H3Cit) and the
release of DNA as neutrophil extracellular traps (NETs). The overall goal of the research is to study the role
PAD4 in inflammatory bowel disease (IBD). This proposal aims to systematically elucidate the role of PAD4-
mediated release of H3Cit and NETs during IBD. Three specific aims are proposed, each of which investigates
the molecular underpinnings by which PAD4 influence gut health and disease. The three aims are interrelated,
independently achievable and would systematically characterize: (i) the role of NETs in murine models of IBD,
(ii) the adverse consequence of PAD4-deficiency in potentiating the ‘spillover’ of neutrophil granule proteins and
(iii) the significance of NETs in preventing bacterial encroachment on the mucosa, that otherwise can perpetuate
intestinal inflammation.
项目摘要
2020年,约有160万美国人被证实患有炎症性肠病(IBD)。
并且预计在美国每年诊断出多达70,000例IBD新病例。IBD
包括影响胃肠道(GI)的慢性复发性炎性疾病,例如克罗恩病
疾病和溃疡性结肠炎。在参与IBD的各种免疫细胞中,嗜中性粒细胞不仅是IBD的免疫细胞,
第一反应细胞类型的炎症,但也参与限制炎症和促进伤口修复。
值得注意的是,缺乏关于肽基精氨酸脱亚胺酶-4的粘膜保护作用的文献
(PAD 4),其主要功能是促进瓜氨酸化组蛋白3(H3Cit)的生成,
作为中性粒细胞胞外陷阱(NET)释放DNA。本研究的总体目标是研究
炎症性肠病(IBD)中的PAD 4。本研究旨在系统地阐明PAD 4的作用。
在IBD期间介导H3Cit和NET的释放。提出了三个具体目标,每个目标都调查
PAD 4影响肠道健康和疾病的分子基础。这三个目标是相互关联的,
独立可实现的,并将系统地表征:(i)NET在IBD的鼠模型中的作用,
(ii)PAD 4缺陷在增强中性粒细胞颗粒蛋白的“溢出”中的不利后果,
(iii)NET在防止细菌侵入粘膜方面的重要性,否则可能使粘膜永久化
肠道炎症
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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MATAM VIJAY-KUMAR其他文献
MATAM VIJAY-KUMAR的其他文献
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{{ truncateString('MATAM VIJAY-KUMAR', 18)}}的其他基金
Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma
膳食纤维与肠道微生物群在肝细胞癌中的相互作用
- 批准号:
10163812 - 财政年份:2017
- 资助金额:
$ 43.69万 - 项目类别:
Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma
膳食纤维与肠道微生物群在肝细胞癌中的相互作用
- 批准号:
9766108 - 财政年份:2017
- 资助金额:
$ 43.69万 - 项目类别:
Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma
膳食纤维与肠道微生物群在肝细胞癌中的相互作用
- 批准号:
10411391 - 财政年份:2017
- 资助金额:
$ 43.69万 - 项目类别:
Interplay between Dietary Fiber and Gut Microbiota in Hepatocellular Carcinoma
膳食纤维与肠道微生物群在肝细胞癌中的相互作用
- 批准号:
9677541 - 财政年份:2017
- 资助金额:
$ 43.69万 - 项目类别:
Role of Lipocalin 2 Inflammatory Bowel Disease
脂质运载蛋白 2 在炎症性肠病中的作用
- 批准号:
8726982 - 财政年份:2013
- 资助金额:
$ 43.69万 - 项目类别:
Role of Lipocalin 2 Inflammatory Bowel Disease
脂质运载蛋白 2 在炎症性肠病中的作用
- 批准号:
8577770 - 财政年份:2013
- 资助金额:
$ 43.69万 - 项目类别:
Role of stearoyl CoA desaturase-1 in TLR5 KO mice colitis and metabolic syndrome
硬脂酰辅酶A去饱和酶-1在TLR5 KO小鼠结肠炎和代谢综合征中的作用
- 批准号:
8459998 - 财政年份:2012
- 资助金额:
$ 43.69万 - 项目类别:
Role of stearoyl CoA desaturase-1 in TLR5 KO mice colitis and metabolic syndrome
硬脂酰辅酶A去饱和酶-1在TLR5 KO小鼠结肠炎和代谢综合征中的作用
- 批准号:
8278779 - 财政年份:2012
- 资助金额:
$ 43.69万 - 项目类别:
Role of stearoyl CoA desaturase-1 in TLR5 KO mice colitis and metabolic syndrome
硬脂酰辅酶A去饱和酶-1在TLR5 KO小鼠结肠炎和代谢综合征中的作用
- 批准号:
8776093 - 财政年份:2012
- 资助金额:
$ 43.69万 - 项目类别:
Role of Adaptive Immunity in the Development of Colitis in TLR5 Deficient Mice
适应性免疫在 TLR5 缺陷小鼠结肠炎发展中的作用
- 批准号:
8370147 - 财政年份:2009
- 资助金额:
$ 43.69万 - 项目类别:
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