Host-derived extracellular vesicles in inflammatory caspase activation
宿主来源的细胞外囊泡在炎症半胱天冬酶激活中的作用
基本信息
- 批准号:9973550
- 负责人:
- 金额:$ 41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-01-16 至 2024-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAlbuminsAntibioticsBacteriaBacterial InfectionsBindingBiochemicalBloodBlood CirculationCASP1 geneCD14 geneCD47 geneCRISPR screenCaspaseCell DeathCell FractionationCell WallCell membraneCell surfaceCellsChronicCleaved cellCommunicable DiseasesComplementComplexConfocal MicroscopyCoupledCre-LoxPCrystallizationCytosolDetectionDevelopmentDiseaseDistantElectronsEndosomesEndothelial CellsEventExtracellular SpaceFamilyFlagellinFlow CytometryGenetic TranscriptionGerm LinesHMGB1 geneHost DefenseHumanImageImmuneImmune responseImmunologic SurveillanceIn SituIn VitroInfectionInflammasomeInflammationInflammatoryInflammatory ResponseInnate Immune SystemIntegration Host FactorsInterleukin-1Interleukin-1 betaInterleukin-18KnowledgeLeaky GutLifeLipidsLiteratureLocationLyticMass Spectrum AnalysisMediatingMembraneMethodsMicroscopicMolecularMultiprotein ComplexesMusMutant Strains MiceMyeloid CellsNucleic AcidsOutcomePathway interactionsPatternPattern recognition receptorPerforationPharmaceutical PreparationsPhysiologyPlayProteinsRNARegulationRoleSepsisSignal TransductionStructureTLR4 geneToxinTranslational ActivationUric AcidVDAC1 geneVesicleVirusWorkbasecell typecytokinedefined contributionextracellular vesiclesimmunoregulationin vivoinsightlipopolysaccharide-binding proteinmicrobialpathogenresponsevirtual
项目摘要
Inflammasome related caspases such as caspase-1, caspase-4, and caspase-11 are a subset of
the caspase family specialized in executing a lytic form of cell death and IL-1 cytokine-based
inflammatory response. The activation of these inflammatory caspases is strongly coupled to
innate immune detection of infections and cellular perturbations via canonical and noncanonical
inflammasomes. Inflammasomes are multiprotein complexes in the cytosol assembled in
response to wide variety of pathogen-associated molecular patterns (PAMPs) including nucleic
acids, toxins, flagellin, and cell wall components and endogenous danger signals (danger-
associated molecular patterns, or DAMPs) such as ATP and uric acid crystals. The assembly of
inflammasome complex leads to the autoproteolytic activation of inflammatory caspases.
Enzymatically active versions of inflammatory caspases activate a pore forming protein called
gasdermin D, which lyses the cells via plasma membrane perforation. Active caspase-1 also
cleaves the inflammatory cytokines pro-IL-1β and pro-IL-18 into their active forms. Inflammatory
caspases are important for initiating the inflammatory response against a wide variety of
pathogens including bacteria and viruses. Inflammatory caspases also play crucial roles in sepsis,
a major life-threatening condition associated with infections. Extracellular vesicles (EVs) are
membrane-bound structures abundantly released by our living cells into the extracellular space.
EVs are packaged with proteins, lipids, and RNAs, and EVs have emerged as a crucial mode of
inter-cellular transfer of all three cargoes. EV-cargoes are functional and modulate the physiology
of the recipient cells. However, the role of EVs in the inflammasome signaling is poorly
understood. This proposal seeks to comprehensively address this critical knowledge gap in three
specific aims. Aim 1 will characterize the impact of host-derived EVs on inflammatory caspase
activation by PAMPs. Aims 2 and 3 will demonstrate the molecular and cellular mechanisms by
which the host-derived EVs regulate PAMP-activation of inflammatory caspases. In summary, this
proposal will reveal a new role for host-derived EVs in inflammasome responses in the context of
host defense with great implications for human infectious diseases and sepsis.
炎症体相关的caspase,如caspase-1、caspase-4和caspase-11是
Caspase家族专门执行一种溶解形式的细胞死亡和基于IL-1的细胞因子
炎症反应。这些炎症性半胱氨酸酶的激活与
通过规范和非规范对感染和细胞扰动的先天免疫检测
炎症性小体。炎性小体是胞浆中的多蛋白复合体,组装在
对多种病原体相关分子模式(PAMP)的反应,包括核
酸、毒素、鞭毛和细胞壁成分以及内源性危险信号(危险-
相关的分子模式或阻尼物),如三磷酸腺苷和尿酸结晶。组装的
炎症体复合体导致炎性半胱氨酸酶的自身蛋白分解激活。
具有酶活性的炎性半胱氨酸酶激活一种名为
Gasdermin D,通过质膜穿孔裂解细胞。激活的caspase-1也
将炎性细胞因子前-IL-1β和前-IL-18分解为其活性形式。炎症性
半胱氨酸天冬氨酸氨基转移酶对于启动对多种
病原体包括细菌和病毒。炎性半胱氨酸蛋白酶在脓毒症中也起着关键作用,
一种与感染相关的危及生命的主要疾病。细胞外小泡(EVS)是
我们的活细胞将大量的膜结合结构释放到细胞外空间。
电动汽车包装有蛋白质、脂质和RNA,电动汽车已经成为一种重要的
所有三种货物的细胞间转移。EV-Cargo具有功能,并调节生理
受体细胞的数量。然而,EVS在炎症体信号转导中的作用很差。
明白了。这项建议寻求在三个方面全面解决这一关键的知识差距
明确的目标。目标1将描述宿主来源的EVS对炎性caspase的影响
由PAMP激活。目标2和目标3将通过以下方式演示分子和细胞机制
宿主来源的EVS调节炎症caspase的PAMP激活。总而言之,这是
该提案将揭示宿主来源的EV在炎症体反应中的新角色
宿主防御对人类传染病和败血症具有重要意义。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Vijay Rathinam其他文献
Vijay Rathinam的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Vijay Rathinam', 18)}}的其他基金
New roles of IFN-inducible OAS proteins in innate immune defense against bacterial infections
IFN诱导的OAS蛋白在针对细菌感染的先天免疫防御中的新作用
- 批准号:
10649771 - 财政年份:2023
- 资助金额:
$ 41万 - 项目类别:
Host-derived extracellular vesicles in inflammatory caspase activation
宿主来源的细胞外囊泡在炎症半胱天冬酶激活中的作用
- 批准号:
10535447 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Host-derived extracellular vesicles in inflammatory caspase activation
宿主来源的细胞外囊泡在炎症半胱天冬酶激活中的作用
- 批准号:
10318094 - 财政年份:2020
- 资助金额:
$ 41万 - 项目类别:
Cytosolic Immune Surveillance During Bacterial Infections
细菌感染期间的细胞质免疫监视
- 批准号:
10416062 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Cytosolic Immune Surveillance During Bacterial Infections
细菌感染期间的细胞质免疫监视
- 批准号:
10306046 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Cytosolic Immune Surveillance During Bacterial Infections
细菌感染期间的细胞质免疫监视
- 批准号:
10625492 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Cytosolic Immune Surveillance During Bacterial Infections
细菌感染期间的细胞质免疫监视
- 批准号:
9225153 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
相似海外基金
Exploiting and enhancing IgE-binding epitopes of the 2S albumins of peanuts and tree nuts
利用和增强花生和坚果 2S 白蛋白的 IgE 结合表位
- 批准号:
10685312 - 财政年份:2021
- 资助金额:
$ 41万 - 项目类别:
Exploiting and enhancing IgE-binding epitopes of the 2S albumins of peanuts and tree nuts
利用和增强花生和坚果 2S 白蛋白的 IgE 结合表位
- 批准号:
10490872 - 财政年份:2021
- 资助金额:
$ 41万 - 项目类别:
Exploiting and enhancing IgE-binding epitopes of the 2S albumins of peanuts and tree nuts
利用和增强花生和坚果 2S 白蛋白的 IgE 结合表位
- 批准号:
10345963 - 财政年份:2021
- 资助金额:
$ 41万 - 项目类别:
Development of Highly Functionalized Serum Albumins as Boron Delivery Carries to Tumor for Neutron Capture Therapy
开发高功能化血清白蛋白作为硼输送至肿瘤以进行中子捕获治疗
- 批准号:
17H02202 - 财政年份:2017
- 资助金额:
$ 41万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Studies on Asymmetric Nitroaldol Reaction using mutant albumins
突变体白蛋白不对称硝醛醇反应的研究
- 批准号:
16K05706 - 财政年份:2016
- 资助金额:
$ 41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
SPIN LABELING STUDIES OF NORMAL RECOMBINANT & MUTANT HUMAN SERUM ALBUMINS
正常重组的旋转标记研究
- 批准号:
6118869 - 财政年份:1999
- 资助金额:
$ 41万 - 项目类别:
COPPER BINDING OF COMMERCIAL, NORMAL RECOMBINANT, & MUTANT HUMAN SERUM ALBUMINS
商业、正常重组的铜结合,
- 批准号:
6118864 - 财政年份:1999
- 资助金额:
$ 41万 - 项目类别:
Structure and Metabolism of the Serum Albumins Characteristic of Bisalbuminemia in Fowl
家禽双清蛋白血症血清白蛋白的结构与代谢特征
- 批准号:
67B6472 - 财政年份:1967
- 资助金额:
$ 41万 - 项目类别:
Structure and Metabolism of the Serum Albumins Characteristic of Bisalbuminemia
双清蛋白血症血清白蛋白的结构和代谢特征
- 批准号:
65B3344 - 财政年份:1965
- 资助金额:
$ 41万 - 项目类别: