Diversity & racial disparity in fetal membrane cytokine signature during infectio
多样性
基本信息
- 批准号:8239899
- 负责人:
- 金额:$ 8.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-03-08 至 2014-02-28
- 项目状态:已结题
- 来源:
- 关键词:AccountingAfrican AmericanAmniotic FluidAnti-Bacterial AgentsAnti-Inflammatory AgentsAnti-inflammatoryAsiansAutologousBacteriaBacterial InfectionsBiochemical PathwayBiological MarkersBirthCaucasiansCaucasoid RaceComplexComplicationConceptionsConditioned Culture MediaCulture MediaDiseaseEquilibriumEscherichia coliEtiologyEventFetal MembranesFetusFunctional disorderGeneticHeterogeneityHumanIL8 geneImmune responseIn VitroInduced LaborInfectionInfectious Pregnancy ComplicationsInflammationInflammatoryInflammatory ResponseInterventionKineticsLaboratoriesMediatingMediator of activation proteinMembraneMolecularMycoplasma hominisNeonatal MortalityOrganPacific Island AmericansPathway interactionsPatientsPatternPilot ProjectsPorphyromonas gingivalisPregnancyPremature BirthPremature LaborProductionPropertyRaceRepeat Cesarean SectionReportingResistanceSeriesSourceStreptococcus Group BSyndromeSystemTestingTissuesTocolytic AgentsUreaplasma urealyticum biovar 1Uterine ContractionWeightWomanantimicrobialchemokinecytokinefetalintraamniotic infectionmicrobialneonatal morbiditypathogenpreterm premature rupture of membranespublic health relevanceracial differenceresponse
项目摘要
DESCRIPTION (provided by applicant): Spontaneous preterm birth (PTB - <birth before 37 weeks gestation) is a major complication of pregnancy and infection is associated with ~ 50% of the cases. Although PTB has a multifactorial etiology, intraamniotic infection (IAI) and the resulting host (maternal and fetal) inflammatory response is a major component of the disease. Microbial factors are thought to evoke a series of events that compromise the immunological privileges that the fetus enjoys from conception until parturition by stimulating the production proinflammatory cytokines and chemokines that induce labor; however, the immune response is not generalizable. This suggests that initiation of labor may depend on the type of immune response to the type of pathogen. Other tissue and bacterial factor-specific cytokine response have also been reported. Not all cytokines, however, seem to activate the downstream mediators that cause labor and preterm birth suggesting that the biomolecular pathways from infection to preterm birth are complex and that patient-specific interventions targeted to a particular molecular mechanism of preterm birth may be necessary. Understanding the infectious etiology and pathophysiology of PTB is further complicated by disproportionately higher rate of infection and PTB rates in African-Americans than Caucasians. Racial differences in biomarker concentrations are expected to contribute to racial disparity. Furthermore, amniotic fluid consists of multiple antimicrobial factors and the concentration and regulatory mechanisms of these factors are also expected to differ in response to specific IAI and also in different races. Therefore, we hypothesize that host immune response and biochemical pathways of labor are not generalizable but differ between specific bacteria associated with IAI and race. In addition, we hypothesize that the immunomodulatory effects of amniotic fluid is also dependent on bacterial species and maternal race. We will test our hypotheses through the following specific aims; Specific Aim 1: To test the differences in the TH1/TH2 and proinflammatory cytokine/chemokine (IL-8) response and kinetics by normal human fetal membranes exposed to common intraamniotic pathogens including: Ureaplasma parvum, Mycoplasma hominis, E. coli, Group B Streptococcus, P. gingivalis and G. vaginalis. Specific Aim 2: To determine if there are racial differences in TH1/TH2 cytokine signature produced by fetal membranes in response to bacterial species listed above in Aim 1. Specific Aim 3: To test the anti-inflammatory properties of amniotic fluid in maintaining a balanced cytokine response.
PUBLIC HEALTH RELEVANCE: Microbial invasion of the intraamniotic cavity and intraamniotic infections and inflammation mediated by a switch in the TH1/TH2 cytokine pattern favoring a proinflammatory response are commonly associated with spontaneous preterm birth. Disproportionately higher rate of infection and preterm births in African Americans and increasing rate of infection associated preterm birth suggest that the infection associated pathophysiologic pathways and biomarkers may not be generalizable and each bacterium may produce their own inflammatory signature and racial disparity will be associated with biomarker profile. In this RO3 application, a pilot study is planned using an in vitro organ explant system for fetal membranes we plan to test differential inflammatory response and racial disparity associated with common intraamniotic pathogens.
描述(由申请人提供):自发性早产(PTB - <妊娠 37 周前出生)是妊娠的主要并发症,约 50% 的病例与感染有关。尽管 PTB 具有多因素病因,但羊膜内感染 (IAI) 和由此产生的宿主(母体和胎儿)炎症反应是该疾病的主要组成部分。人们认为,微生物因素会刺激促炎性细胞因子和引产趋化因子的产生,从而引发一系列损害胎儿从受孕到分娩所享有的免疫特权的事件;然而,免疫反应并不具有普遍性。这表明分娩的开始可能取决于对病原体类型的免疫反应类型。还报道了其他组织和细菌因子特异性细胞因子反应。然而,并非所有细胞因子似乎都会激活导致分娩和早产的下游介质,这表明从感染到早产的生物分子途径是复杂的,并且针对早产的特定分子机制的患者特异性干预措施可能是必要的。由于非裔美国人的感染率和 PTB 发生率明显高于白人,因此了解 PTB 的感染性病因和病理生理学变得更加复杂。生物标志物浓度的种族差异预计会导致种族差异。此外,羊水由多种抗菌因子组成,这些因子的浓度和调节机制预计也会因特定 IAI 的反应而有所不同,并且在不同种族中也有所不同。因此,我们假设宿主免疫反应和分娩的生化途径不可概括,但与 IAI 和种族相关的特定细菌之间存在差异。此外,我们假设羊水的免疫调节作用还取决于细菌种类和母体种族。我们将通过以下具体目标来检验我们的假设;具体目标 1:测试暴露于常见羊膜内病原体的正常人胎膜的 TH1/TH2 和促炎细胞因子/趋化因子 (IL-8) 反应和动力学的差异,这些病原体包括:微小解脲支原体、人型支原体、大肠杆菌、B 组链球菌、牙龈卟啉单胞菌和阴道杆菌。具体目标 2:确定胎膜响应目标 1 中列出的细菌种类而产生的 TH1/TH2 细胞因子特征是否存在种族差异。具体目标 3:测试羊水在维持平衡中的抗炎特性细胞因子反应。
公共卫生相关性:微生物侵入羊膜腔以及由有利于促炎症反应的 TH1/TH2 细胞因子模式转换介导的羊膜内感染和炎症通常与自发性早产有关。非裔美国人的感染率和早产率不成比例地较高,以及与早产相关的感染率不断增加,表明感染相关的病理生理途径和生物标志物可能无法概括,每种细菌可能产生自己的炎症特征,种族差异将与生物标志物谱相关。在此 RO3 应用中,计划使用胎膜体外器官外植体系统进行试点研究,我们计划测试与常见羊膜内病原体相关的差异炎症反应和种族差异。
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Systematic review of p38 mitogen-activated kinase and its functional role in reproductive tissues.
p38 丝裂原激活激酶及其在生殖组织中的功能作用的系统评价。
- DOI:
- 发表时间:2018
- 期刊:
- 影响因子:0
- 作者:Sheller;Richardson, Lauren;Martin, Laura;Jin, Jin;Menon, Ramkumar
- 通讯作者:Menon, Ramkumar
Programmed Fetal Membrane Senescence and Exosome-Mediated Signaling: A Mechanism Associated With Timing of Human Parturition.
程序性胎儿膜衰老和外泌体介导的信号传导:与人类分娩时间相关的机制。
- DOI:
- 发表时间:2017
- 期刊:
- 影响因子:0
- 作者:Menon, Ramkumar;Mesiano, Sam;Taylor, Robert N
- 通讯作者:Taylor, Robert N
Amniotic fluid and maternal race influence responsiveness of fetal membranes to bacteria.
羊水和母体种族影响胎膜对细菌的反应性。
- DOI:
- 发表时间:2012-12
- 期刊:
- 影响因子:3.4
- 作者:Peltier, Morgan R;Drobek, Cayce O;Bhat, Geeta;Saade, George;Fortunato, Stephen J;Menon, Ramkumar
- 通讯作者:Menon, Ramkumar
Oxidative stress-induced TGF-beta/TAB1-mediated p38MAPK activation in human amnion epithelial cells.
氧化应激诱导人羊膜上皮细胞中 TGF-β/TAB1 介导的 p38MAPK 激活。
- DOI:
- 发表时间:2018
- 期刊:
- 影响因子:3.6
- 作者:Richardson, Lauren;Dixon, Christopher Luke;Aguilera;Menon, Ramkumar
- 通讯作者:Menon, Ramkumar
Fetal membrane biomarker network diversity and disease functions induced by intra-amniotic pathogens.
羊膜内病原体诱导的胎膜生物标志物网络多样性和疾病功能。
- DOI:
- 发表时间:2013-02
- 期刊:
- 影响因子:0
- 作者:Bhat, Geeta;Peltier, Morgan R;Syed, Tariq Ali;Drobek, Cayce O;Saade, George;Menon, Ramkumar
- 通讯作者:Menon, Ramkumar
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RAMKUMAR MENON其他文献
RAMKUMAR MENON的其他文献
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{{ truncateString('RAMKUMAR MENON', 18)}}的其他基金
Engineering Fetal Cell Exosomes to contain HMGB1: Its trafficking and role as an inflammatory activator in uterine cells
工程化胎儿细胞外泌体以含有 HMGB1:其运输及其在子宫细胞中作为炎症激活剂的作用
- 批准号:
9883717 - 财政年份:2019
- 资助金额:
$ 8.18万 - 项目类别:
Static state of epithelial mesenchymal transition in fetal membrane cells: a novel inflammatory pathway to parturition
胎儿膜细胞上皮间质转化的静态:一种新的分娩炎症途径
- 批准号:
9893012 - 财政年份:2019
- 资助金额:
$ 8.18万 - 项目类别:
Fetal Cell Senescence Signals Initiation of Parturition
胎儿细胞衰老标志着分娩的开始
- 批准号:
9901548 - 财政年份:2016
- 资助金额:
$ 8.18万 - 项目类别:
Fetal Cell Senescence Signals Initiation of Parturition
胎儿细胞衰老标志着分娩的开始
- 批准号:
9276045 - 财政年份:2016
- 资助金额:
$ 8.18万 - 项目类别:
Fetal Cell Senescence Signals Initiation of Parturition
胎儿细胞衰老标志着分娩的开始
- 批准号:
9454525 - 财政年份:2016
- 资助金额:
$ 8.18万 - 项目类别:
Diversity & racial disparity in fetal membrane cytokine signature during infectio
多样性
- 批准号:
8373458 - 财政年份:2011
- 资助金额:
$ 8.18万 - 项目类别:
Diversity & racial disparity in fetal membrane cytokine signature during infectio
多样性
- 批准号:
8031700 - 财政年份:2011
- 资助金额:
$ 8.18万 - 项目类别:
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