Middle Ear Epithelial Response to Cytokine Stimulation

描述(摘自申请人摘要)：中耳炎是最常见的 在美国就诊的儿科患者的诊断 各州。尽管中耳炎很普遍，但其发病的可能性， 因其治疗而产生的巨额医疗支出以及 抗菌素耐药性带来的治疗挑战与日俱增 仍不清楚细胞和分子免疫学和炎症性 这一疾病过程中发生的事件。已知中车上皮扮演着一种 细胞因子在中耳炎病理生理学中的重要作用 介导性炎症反应。细胞培养技术的最新进展 能够对培养的中耳上皮进行研究，并提供 机制以加深我们对细胞和分子事件的理解 中耳炎。 这个项目的目标是检验培养的中耳 上皮细胞(MEEC)暴露于炎性细胞因子肿瘤坏死 因子-阿尔法。(肿瘤坏死因子-α)、白介素1β(IL-1β)、白介素6(IL-6) 6)和白介素8(IL-8)将在以下方面发生变化：1)粘蛋白 分泌物(MGP)；2)粘蛋白基因表达；3)形态。使用单元格和 分子生物学技术，上皮细胞对该阵列的反应差异 会比较炎性细胞因子和阻断特异性的能力 这些细胞因子通过使用细胞因子抑制剂带来的变化将 接受检查。肿瘤坏死因子-α、白细胞介素1β、白细胞介素6的受体后信号转导 此外，还将检测IL-8对MEEC MGP分泌的影响。 理解细胞因子-中耳参与的细胞和分子事件 上皮相互作用、MGP产生、粘蛋白基因表达和信号转导 这些途径可能会为中耳炎提供新的有效的治疗方法。 细胞因子途径的调节和中间产物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.