Bacterial Products as Potentiaters of AD

细菌性皮肤感染，尤其是由金黄色葡萄球菌引起的感染，既可引发也可传播。 许多炎症性皮肤病，特别是特应性皮炎(AD)。它们的作用机制 这种情况的发生尚不清楚，但许多证据表明，生物活性参与了 葡萄球菌细菌产物，如超抗原毒素、阿尔法毒素和细胞壁 脂蛋白脂磷壁酸(LTA)。这些葡萄球菌产品的刺激能力 角质形成细胞中细胞因子的产生可能为葡萄球菌皮肤提供一种机制 感染会加重阿尔茨海默病。来自我们小组的初步和发表的数据都表明，脂质 介体血小板激活因子(PAF)可以调节这些细菌产物对 角质形成细胞细胞因子的产生。计划有三个具体目标来帮助定义该机制(S) 通过细菌产品使皮肤病恶化，这将使新的治疗策略成为可能 感染性特应性皮炎患者。第一个目标将定义这些指标的水平 葡萄球菌产品在临床感染的AD皮损上，并产生生物活性洗涤液 用于本项目和项目2的进一步研究。 第二个目标将使用两个新的模型系统，包括PAF-R和Toll受体-阳性和阴性 表皮细胞确定PAF-R与Toll样受体在细菌产物介导中的作用 细胞因子的产生。第三个目标将检查细菌产品的能力 在野生型和新型特应性疾病小鼠模型中诱导皮肤炎症 (StatGVT小鼠)。PAF-R-/-和MyD88-/-小鼠将用于定义PAF和类似Toll的角色 在这些过程中的受体系统。

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.