Alcohol Effects on Gene and Cytokine Expression of Human Airway Epithelia

描述（由申请人提供）：过量的酒精摄入通常会导致组织损伤，导致严重的医学疾病。长期以来，酗酒者容易感染多种传染病，特别是肺部感染。气道上皮细胞代表第一道防线。它们不仅提供结构屏障和机械防御机制，而且通过分泌各种细胞因子来动员和调节宿主的防御机制，积极响应细菌的挑战。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伤的细胞机制至关重要。我们假设酒精暴露改变了气道上皮细胞对细菌入侵的基因组和细胞因子反应，从而损害了正常的气道防御机制。这些作用可能使上皮细胞易受细菌感染和损伤。这个R21的建议是使用一个独特的空气-空气-液体界面气道上皮细胞培养模型和两个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的基因表达和细胞因子的产生。提出了以下三个具体目标。具体目标1：使用细胞因子多重阵列方法确定酒精对人气道上皮细胞hemokine产生的细胞因子和c趋化因子的影响;具体目标2：通过基因芯片分析确定酒精对人气道上皮细胞基因表达谱的影响;具体目标3：研究酒精对气道上皮细胞活力和完整性的影响。通过具体目标的完成，我们期望获得关于酒精如何在分子和细胞水平上导致人类气道损伤的知识，这可能使患者易患酒精相关的肺部感染和损伤。这项研究可能为开发控制或改变酒精滥用结果的潜在治疗方法提供信息。

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.