Middle Ear Epithelial Response to Cytokine Stimulation

描述（来自申请人摘要）：中耳炎是最常见的 在美国，因疾病就诊的儿科患者的诊断 states. 尽管中耳炎的流行，其潜在的发病率， 巨大的医疗保健支出所造成的治疗和 抗微生物药物耐药性带来的治疗挑战越来越大， 目前尚不清楚细胞和分子免疫学和炎症 在这个疾病过程中。 中车上皮细胞是众所周知的， 通过细胞因子在中耳炎病理生理学中的重要作用 介导的炎症反应。细胞培养技术的最新进展 使研究中耳上皮细胞的文化，并提供了一个 机制，以进一步了解细胞和分子事件， 中耳炎 本课题的目的是验证培养中耳 上皮细胞（MEEC）暴露于炎性细胞因子肿瘤坏死 α因子 （TNF-α）、白细胞介素-1 β（IL-1 β）、白细胞介素-6（IL-6）、白细胞介素-1 β（IL-1 β）、白细胞介素-1 β（IL-1 β）、白细胞介素-1 β（IL-2 β）、白细胞介素-1 β（IL-3 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-6 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-6 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-6 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-6 β）、白细胞介素-1 β（IL-4 β）、白细胞介素-1 β（IL-6 β） 6)白细胞介素-8（IL-8）将表现出以下变化：1）粘糖蛋白 分泌（MGP），2）粘蛋白基因表达和3）形态学。 使用Cell和 分子生物学技术，上皮细胞对该阵列的反应差异 的炎症细胞因子的能力进行比较，并阻断特异性 通过使用细胞因子抑制剂由这些细胞因子引起的变化将 接受检查。TNF-α、IL-1 β、IL-6的受体后信号转导 和IL-8对MEEC MGP分泌的影响。 了解参与中耳炎的细胞和分子事件 上皮相互作用，MGP产生，粘蛋白基因表达和信号传导 通路将潜在地允许用于耳炎的新颖且有效的治疗 通过调节细胞因子途径和MGP的产生， 耳上皮细胞

DESCRIPTION (from applicant's abstract): Otitis media is the most common diagnosis in pediatric patients who visit physicians for illness in the United States. Despite the prevalence of otitis media, its potential for morbidity, the enormous health care expenditures resulting from its treatment and the increasing therapeutic challenges imposed by antimicrobial resistance, much is still unknown about the cellular and molecular immunologic and inflammatory events in this disease process. Middle car epithelium is known to play a significant role in the pathophysiology of otitis media through a cytokine mediated inflammatory response. Recent advances in cell culture techniques have enabled investigations of middle ear epithelium in culture and provide a mechanism to further our understanding of the cellular and molecular events in otitis media. The goals of this project are to test the hypothesis that cultured middle ear epithelial cells (MEEC) exposed to the inflammatory cytokines tumor necrosis factor-alpha. (TNF-alpha), interleukin- 1 beta (IL- 1 beta), interleukin-6 (IL- 6) and interleukin-8 (IL-8) will exhibit changes in: 1) mucoglycoprotein secretion (MGP), 2) mucin gene expression and 3) morphology. Using cell and molecular biology techniques, differences in epithelial response to this array of inflammatory cytokines will be compared and the ability to block the specific changes brought about by these cytokines by the use of cytokine inhibitors will be examined. Post-receptor signal transduction of TNF-alpha, IL- 1 beta, IL-6 and IL-8 in regards to MEEC MGP secretion will also be examined. Understanding the cellular and molecular events involved in cytokine-middle ear epithelial interactions, MGP production, mucin gene expression and signaling pathways will potentially allow for novel and efficacious treatments for otitis media through modulation of the cytokine pathway and MGP production by middle ear epithelial cells.