Alcohol Effects on Gene and Cytokine Expression of Human Airway Epithelia

酒精对人气道上皮基因和细胞因子表达的影响

基本信息

批准号：
7848648
负责人：
GUOSHUN WANG
金额：
$ 2.6万
依托单位：
LSU HEALTH SCIENCES CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-06-22 至 2009-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7848648
关键词：
Adult Respiratory Distress Syndrome Affect Air Alcohol abuse Alcoholic Liver Diseases Alcohols Apical Apoptosis Bacterial Infections Cell Survival Cells Cirrhosis Communicable Diseases Cytokine Gene Defense Mechanisms Development Dextrans Disease Dose Epithelial Epithelial Cells Epithelium Ethanol Fingerprint Gene Cluster Gene Expression Gene Expression Profile Genes Genomics Heavy Drinking Host Defense Human Human Genome Infection Injury Invaded Iodine Klebsiella pneumonia bacterium Knowledge Liquid substance Lung Measures Mechanics Medical Modeling Molecular Necrosis Outcome Pancreatitis Pathway interactions Patients Permeability Predisposition Production Propidium Research Resistance Staining method Stains Surface Suspension substance Suspensions System Technology Testing Therapeutic Time Tissues airway epithelium alcohol effect alcohol exposure alcohol response annexin A5 chemokine cytokine dextran insight novel pathogen research study response synthetic polymer Bioplex therapeutic development

项目摘要

DESCRIPTION (provided by applicant): Excessive alcohol intake often causes tissue injury, leading to severe medical disorders. It has long been recognized that alcohol abusers are susceptible to a wide range of infectious diseases, particularly pulmonary infection infections. Airway epithelia represent the first line of defense. They not only provide structural barriers and mechanical defense mechanisms, but also respond actively to bacterial challenge by secreting various cytokines to mobilize and modulate the host defens defense. Therefore, understanding alcohol effects on airway epithelial cells is critical to elucidate the cellular mechanisms of alcohol damage to airways. We hypothesize that alcohol exposure alters genomic and cytokine responses of airway epithelia to bacteri bacterial invasion and thus impairs the normal airway defense al mechanisms. The effects may render the epithelia susceptible to bacterial infection and injury. This R21 proposal is to use one unique air air-liquid interface airway epithelial culture model and two powerful gene and cytokine analysis approaches to investigate how alcohol affects airway epithelial cell gene expressions and cytokine productions. Three specific aims are proposed as follows. Specific Aim 1: to determine the effect of alcohol on cytokine and c chemokine production by human airway epithelial cells hemokine using the cytokine multiplex array approach; Specific Aim 2: to determine the effect of alcohol on gene expression profile of human airway epithelial cells by GeneChip analysis; Specific Aim 3: to study the effects of alcohol on airway epithelial viability and integrity. Through completion of the specific aims, we expect to gain knowledge on how alcohol leads to human airway damage at the molecular and cellular levels, which may predispose patients to al alcohol cohol-associated pulmonary infections and injury. This research may provide information for the development of potential therapeutics to control or modify outcomes of alcohol abuse.

描述（由申请人提供）：过量的酒精摄入量通常会导致组织损伤，导致严重的医疗疾病。长期以来，人们已经认识到，滥用酗酒者容易受到广泛的感染性疾病，尤其是肺部感染。气道上皮是第一道防线。他们不仅提供结构性障碍和机械防御机制，而且还通过分泌各种细胞因子来动员和调节宿主防御防御，从而积极应对细菌挑战。因此，了解酒精对气道上皮细胞的影响对于阐明酒精对气道损害的细胞机制至关重要。我们假设酒精暴露会改变气道上皮菌对细菌侵袭的基因组和细胞因子反应，从而损害正常的气道防御机制。这种作用可能会使上皮容易受到细菌感染和损伤的影响。该R21提案是使用一种独特的空气液体界面气道上皮培养模型以及两种强大的基因和细胞因子分析方法来研究酒精如何影响气道上皮细胞基因表达和细胞因子生产。提出了三个特定目标，如下所示。具体目的1：确定使用细胞因子多重阵列方法，人类气道上皮细胞易血管对酒精的影响；特定目的2：确定酒精对人类气道上皮细胞基因表达谱的影响；特定目的3：研究酒精对气道上皮生存能力和完整性的影响。通过完成特定目标，我们希望获得有关酒精如何在分子和细胞水平上导致人类气道损害的知识，这可能使患者易患艾尔酒精的肺部相关肺部感染和损伤。这项研究可能会为开发潜在的治疗剂来控制或修改酗酒结果的信息提供信息。