Bacterial Products as Potentiaters of AD

细菌产物作为 AD 的增强剂

• 批准号: 7150325
• 负责人: Jeffrey B. Travers
• 金额: $ 23.41万
• 依托单位: INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7150325
• 关键词: Staphylococcus aureus; Staphylococcus infection; atopic dermatitis; bacteria infection mechanism; bacterial proteins; cytokine; developmental immunology; disease /disorder model; genetically modified animals; host organism interaction; human subject; hypersensitivity; immunomodulators; infant human (0-1 year); inflammation; keratinocyte; laboratory mouse; microorganism immunology; nuclear factor kappa beta; pathologic process; platelet activating factor; preschool child (1-5); skin infection; toll like receptor

Bacterial skin infections, especially by Staphylococcus aureus, can both initiate and propagate many inflammatory skin diseases, particularly atopic dermatitis (AD). The mechanisms by which this occurs are unclear, but many lines of evidence implicate the involvement of biologically active staphylococcal bacterial products such as superantigen toxins, alpha toxin, and the cell-wall lipoprotein lipoteichoic acid (LTA). The ability of these staphylococcal products to stimulate cytokine production in keratinocytes could provide one mechanism by which staphylococcal skin infections worsen AD. Both preliminary and published data from our group indicate that the lipid mediator platelet-activating factor (PAF) can modulate the effects of these bacterial products on keratinocyte cytokine production. Three specific aims are planned to help define the mechanism(s) by which bacterial products worsen skin disease which will allow novel treatment strategies for patients with infected atopic dermatitis. The first objective will define the levels of these staphylococcal products on clinically infected AD lesions, and generate biologically active wash fluid from infected AD lesions for further studies for both this Project as well as for Project 2. The second aim will use two novel model systems with PAF-R and toll-receptor-positive and -negative epidermal cells to define the role of the PAF-R versus toll-like receptors in bacterial productmediated cytokine production. The third objective will examine the ability of bacterial products to induce cutaneous inflammation both in wild-type and a novel mouse model of atopic disease (StatGVT mice). PAF-R-/- and MyD88-/- mice will be used to define the role of the PAF and toll-like receptor system in these processes.

细菌皮肤感染，尤其是金黄色葡萄球菌，既可以启动又可以传播 许多炎症性皮肤病，特别是特应性皮炎（AD）。所在的机制 发生这种情况尚不清楚，但是许多证据表明生物活性的参与 葡萄球菌细菌产物，例如超抗原毒素，α毒素和细胞壁 脂蛋白脂蛋白酸（LTA）。这些葡萄球菌产物刺激的能力 角质形成细胞中的细胞因子产生可以提供一种机制，葡萄球菌皮肤 感染恶化广告。初步和已发布的数据都表明脂质 介体血小板激活因子（PAF）可以调节这些细菌产品对 角质形成细胞细胞因子的产生。计划三个具体目标以帮助定义机制 细菌产物使皮肤病恶化，这将允许新颖的治疗策略 感染特应性皮炎的患者。第一个目标将定义这些水平 临床感染的AD病变上的葡萄球菌产物，并产生生物活性洗涤液 从受感染的AD病变进行该项目以及项目2的进一步研究。 第二个目标将使用PAF-R和TOLL受体阳性和阴性的两个新型模型系统 表皮细胞定义PAF-R与Toll样受体在细菌产物介导的作用 细胞因子产生。第三个目标将检查细菌产品的能力 在野生型和新型小鼠特应性疾病模型中诱发皮肤炎症 （Statgvt小鼠）。 PAF-R - / - 和MyD88 - / - 小鼠将用于定义PAF和类似Toll的作用 这些过程中的受体系统。