Aberrant immunological phenotypes/functions in the progression of early-onset AgP
早发性 AgP 进展中的异常免疫表型/功能
基本信息
- 批准号:7694333
- 负责人:
- 金额:$ 21.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2008
- 资助国家:美国
- 起止时间:2008-09-30 至 2011-08-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAfrican AmericanAgeBacterial AntigensChildClinicalControlled StudyCountyCoupledCytokine GeneDataDefectDiabetes MellitusDiagnosisDiseaseDisease ProgressionGene ExpressionGene Expression RegulationGenetic TranscriptionGeographic LocationsGoalsHealthHeart DiseasesHomeostasisImmuneImmune responseImmune systemIndividualInflammationInflammatoryInflammatory ResponseKnowledgeLeadMediatingMediator of activation proteinMessenger RNAMicroRNAsModelingMolecularNatural ImmunityParentsParticipantPathogenesisPatternPeriodontal DiseasesPeriodontitisPhenotypePlayPregnancy OutcomePrevalenceProcessProductionRaceRegulationResearchResearch Project GrantsRoleSeveritiesSiblingsStrokeTestingTimeTissuesTooth MobilityTooth structureTranslatingUp-Regulationbasechemokinecohortcraniofacialcytokinediabeticearly onsetexperiencegrandparentmacrophagemembermonocytenovel therapeuticsoral bacteriaoral pathogenoral tissuepathogenpreventpublic health relevanceresponsetooth surfacetraittransmission process
项目摘要
DESCRIPTION (provided by applicant): Activated innate immunity and inflammation mediate the pathogenesis of many diseases. New perspectives on the contribution of innate immunity to these diseases, can lead to important new therapeutic considerations and goals for treatment. The overall goal of our research plan is to define immunological mechanisms, aberrant or otherwise, which could be responsible for exacerbation of inflammatory diseases in general. Here we propose to use a model of aggressive periodontal disease (AgP) in which aberrant inflammatory processes are evident. Aggressive periodontitis is a rare, severe and rapidly progressing form of periodontitis usually following a simple pattern of familial transmission with a mean prevalence in the world around 2%3-5. Because the prevalence of aggressive periodontal disease is so low, data about mechanisms of this disease is very scarce and results are based mostly on clinical experience of individual clinicians rather than controlled studies. Interestingly, we have identified a cohort of 47 African-American children in an underserved region of Tallahassee, all within one single health department in Leon County, diagnosed with moderate to severe localized AgP. An important strength of this application is the similarity of the cohort in terms of race, age and pattern of disease coupled with the rarity of the disease and availability of related and unrelated healthy controls. We hypothesize that this cohort harbors aberrant regulation of immunological responses to bacterial pathogens which leads to increased severity and timing of periodontal destruction. Here we propose to investigate regulatory mechanisms of cyto/chemokine expression which directly and indirectly contribute to tissue destruction and periodontal disease progression. The `hyper-responsive' phenotype refers to an increased inflammatory response by the innate immune system, therefore, one objective of this proposal seeks to determine if this underlying defect in the immune response is present in the Tallahassee cohort and if this trait can be elicited in response to periodontal pathogens. Micro RNA (miRNA) regulate pro-inflammatory cytokine mRNA and are up regulated upon LPS stimulation. It is plausible that miRNA regulate cytokine gene expression during periodontal disease in response to LPS stimulation by oral pathogens. Therefore, an additional objective of this proposal is to determine if aberrant expression of miRNA result in dysregulation of cyto/chemokine expression resulting in more aggressive disease progression. Importantly, these data will allow us to contribute greatly to the field of immune regulation, and will spawn multiple research projects in this ever evolving field.
PUBLIC HEALTH RELEVANCE: The immune system is responsible for defending us from multiple types of insult, yet an over-active immune system plays a large role in many disease processes. Therefore, it is the goal of this proposal and our research plan to investigate regulation of the immune response in a model of aggressive periodontal disease in which over-active immune processes are evident and play a significant role in disease progression. Regulation mechanisms deciphered here will be translated to other disease processes which incorporate over-active immune responses.
描述(由申请人提供):激活的先天免疫和炎症介导了许多疾病的发病机理。关于先天免疫对这些疾病的贡献的新观点可能会导致重要的新治疗考虑因素和治疗目标。我们的研究计划的总体目标是定义异常或以其他方式定义免疫机制,这可能导致加剧炎症性疾病。在这里,我们建议使用一种侵袭性牙周疾病(AGP)模型,其中显而易见的炎症过程。侵略性牙周炎是一种罕见,严重且迅速发展的牙周炎形式,通常遵循一种简单的家族传播模式,在世界上平均患病率在2%3-5左右。由于侵袭性牙周疾病的患病率太低,因此有关该疾病机制的数据非常稀缺,结果主要基于个别临床医生的临床经验,而不是对照研究。有趣的是,我们已经确定了在塔拉哈西(Tallahassee)服务不足地区的47名非裔美国儿童组成的队列,所有这些儿童均在莱昂县一个单一卫生部门内,被诊断出患有中度至重度局部AGP。该应用的一个重要优势是,在种族,年龄和疾病模式方面,疾病的罕见性以及相关和无关的健康对照的可用性,同类的相似性。我们假设该队列具有对细菌病原体的免疫反应的异常调节,从而导致严重程度增加和牙周破坏时间。在这里,我们建议研究Cyto/趋化因子表达的调节机制,该机制直接和间接地有助于组织破坏和牙周疾病进展。因此,“超响应性”表型是指先天性免疫系统的炎症反应增加,因此,该提案的一个目的试图确定tallahassee队列中的这种免疫反应中的这种潜在缺陷是否存在,并且是否可以针对周期病原体响应这种特征。微RNA(miRNA)调节促炎性细胞因子mRNA,并在LPS刺激下受到调节。 MiRNA对口服病原体刺激LPS刺激时,miRNA调节牙周疾病期间细胞因子基因的表达。因此,该提案的另一个目标是确定miRNA的异常表达是否导致细胞/趋化因子表达失调,从而导致更具侵略性的疾病进展。重要的是,这些数据将使我们能够为免疫调节领域做出巨大贡献,并在这个不断发展的领域中产生多个研究项目。
公共卫生相关性:免疫系统负责捍卫我们免受多种类型的侮辱,但是过度活跃的免疫系统在许多疾病过程中起着很大的作用。因此,这是该提案的目的和我们的研究计划的目的是在侵袭性牙周疾病模型中调查免疫反应的调节,在侵袭性牙周疾病中,过度活跃的免疫过程显而易见,并在疾病进展中起重要作用。此处解密的调节机制将转化为其他疾病过程,其中包含过度活跃的免疫反应。
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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Shannon Margaret Wallet其他文献
Shannon Margaret Wallet的其他文献
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{{ truncateString('Shannon Margaret Wallet', 18)}}的其他基金
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Genetic regulation of intestinal epithelial cell innate immune signaling in human type 1 diabetes
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Epithelial Cell Function in the Progression of Periodontal Disease
上皮细胞在牙周病进展中的功能
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8851566 - 财政年份:2013
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Epithelial Cell Function in the Progression of Periodontal Disease
上皮细胞在牙周病进展中的功能
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8666633 - 财政年份:2013
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Epithelial Cell Function in the Progression of Periodontal Disease
上皮细胞在牙周病进展中的功能
- 批准号:
8560637 - 财政年份:2013
- 资助金额:
$ 21.98万 - 项目类别:
Aberrant immunological phenotypes/functions in the progression of early-onset AgP
早发性 AgP 进展中的异常免疫表型/功能
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7586001 - 财政年份:2008
- 资助金额:
$ 21.98万 - 项目类别:
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