Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules
乙醇通过 HMGB1、IL-1Beta 和其他免疫信号分子调节中枢和外周免疫反应
基本信息
- 批准号:10004214
- 负责人:
- 金额:$ 13.3万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-09-08 至 2022-08-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAcuteAffectAgonistAlcohol abuseAlcohol consumptionAlcoholic HepatitisAlcoholic Liver DiseasesAlcoholismAlcoholsAutophagocytosisBasic ScienceBiological AssayBody SurfaceBrainBurn injuryCell CommunicationCell Culture SystemCellsCessation of lifeChronicClinicalClinical ResearchCo-ImmunoprecipitationsCompanionsCritical IllnessDataDevelopmentDiseaseDoctor of PhilosophyDoseEnsureEnzymesEthanolFRAP1 geneFlow CytometryFoundationsGlycyrrhizic AcidGoalsHMGB1 geneHourHumanImmuneImmune System DiseasesImmune responseImmune signalingImmune systemIn VitroInflammationInflammatoryInflammatory ResponseInflammatory Response PathwayInjectionsInnate Immune ResponseInnate Immune SystemInterleukin-1Interleukin-1 betaIntestinal permeabilityKineretLabelLaboratoriesLeadLearningLinkLipidsLiverLungMass Spectrum AnalysisMeasuresMediatingMentorsMentorshipMicrogliaModelingMusNatural ImmunityNeurogliaNeuronsOrganOutcomePTEN genePathologyPathway interactionsPatientsPeripheralPharmacotherapyPlasmaPneumoniaPoly I-CProteinsRecording of previous eventsRecoveryResearchResearch PersonnelRoleSecondary toSepsisSeverity of illnessSignal PathwaySignal TransductionSignaling MoleculeSirolimusSliceSpleenStomachTLR3 geneTLR4 geneTechniquesTestingTimeTissuesViralWestern BlottingWorkalcohol effectalcohol exposurealcohol use disordercareercareer developmentcell typecytokineexperimental studyfluorescence imagingimmune activationimmunocytochemistryin vivoinhibitor/antagonistlaboratory experiencemortalityneuroinflammationnovelnovel therapeuticspreventable deathproblem drinkerprotective effectresearch and developmentresponsetranslational scientistuptakevesicular releasewortmannin
项目摘要
Project Summary/Abstract
Alcohol use disorders are third leading cause of preventable death, accounting for
approximately 90,000 preventable deaths each year (Danaei et al 2009). Nearly 50%
deaths are secondary to diseases that are associated with inflammation and aberrant
immune activation such as sepsis and alcoholic liver disease (Mokdad et al 2000).
Recent discoveries find that alcohol activates the innate immune system in both the
CNS and periphery. Thus, understanding the effects of alcohol on the immune system
is critical to form a foundation of discovery leading to the understanding of both the
pathology of alcoholism and numerous alcohol-associated diseases. We have found
recently that alcohol activates the innate immune system through the ‘master regulator’
of innate immunity, HMGB1. In this proposal we aim to investigate the effects of alcohol
on central and peripheral immune activation through HMGB1 and its companion
cytokine IL-. Using in vitro cell culture systems (Aim 1), in vivo experiments (Aim 2-3)
and assessments in human alcoholics, burn patients and alcoholic hepatitis patients
(Aim 4), we hope to gain an understanding of the immune effects of alcohol throughout
the body. I will gain new laboratory experience with real time-PCR, enzyme-linked
immunosorbant assays, co-immunoprecipitation, western blotting, intracerebral AAV5
viral injections, mass spectrometry, immunocytochemistry, and live fluorescent imaging.
We also investigate a novel mechanism of cell-cell communication in this pathology,
alcohol-induced release of pro-inflammatory microparticles. Further, we investigate the
role of the PTEN/PI3K/Akt/mTOR pathway in the immune effects of alcohol, and study
inhibitors of this pathway which may be novel therapeutic options. Our preliminary data
strongly suggest that alcohol causes central and peripheral HMGB1 and IL-1 release
in microparticles through a PTEN/PI3K/Akt/mTOR linked mechanism. This project also
incorporates substantial career development with career and research mentoring from
top tier researchers and clinicians, the learning of new experimental techniques, and
course work to enhance clinical/translational expertise. Co-mentors Fulton T. Crews,
PhD and Bruce Cairns MD provide a depth of basic science, clinical research, and
career development mentorship that will help ensure the successful transition of the
candidate to being a top independent translational researcher.
项目总结/文摘
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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Leon Garland Coleman其他文献
Leon Garland Coleman的其他文献
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{{ truncateString('Leon Garland Coleman', 18)}}的其他基金
Scientific Mentoring and Research Experiences Core
科学指导和研究经验核心
- 批准号:
10541712 - 财政年份:2022
- 资助金额:
$ 13.3万 - 项目类别:
Scientific Mentoring and Research Experiences Core
科学指导和研究经验核心
- 批准号:
10705747 - 财政年份:2022
- 资助金额:
$ 13.3万 - 项目类别:
Ethanol Inhibition of anti-PD-1 Immunotherapy via T-cell Dysfunction and Intestinal Dysbiosis
乙醇通过 T 细胞功能障碍和肠道菌群失调抑制抗 PD-1 免疫治疗
- 批准号:
10218700 - 财政年份:2021
- 资助金额:
$ 13.3万 - 项目类别:
Ethanol Inhibition of anti-PD-1 Immunotherapy via T-cell Dysfunction and Intestinal Dysbiosis
乙醇通过 T 细胞功能障碍和肠道菌群失调抑制抗 PD-1 免疫治疗
- 批准号:
10403618 - 财政年份:2021
- 资助金额:
$ 13.3万 - 项目类别:
Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules
乙醇通过 HMGB1、IL-1Beta 和其他免疫信号分子调节中枢和外周免疫反应
- 批准号:
9314186 - 财政年份:2017
- 资助金额:
$ 13.3万 - 项目类别:
Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules
乙醇通过 HMGB1、IL-1Beta 和其他免疫信号分子调节中枢和外周免疫反应
- 批准号:
9757591 - 财政年份:2017
- 资助金额:
$ 13.3万 - 项目类别:
Ethanol modulate central and peripheral immune responses via HMGB1, IL-1Beta, and other Immune Signaling Molecules
乙醇通过 HMGB1、IL-1Beta 和其他免疫信号分子调节中枢和外周免疫反应
- 批准号:
10238811 - 财政年份:2017
- 资助金额:
$ 13.3万 - 项目类别:
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