Human middle ear cell lines as tools for the Otitis Media research community

项目摘要 中耳炎（OM）影响超过90%的五岁以下儿童，并且是中耳炎的最常见适应症。 儿童的抗菌治疗。OM也是儿童听力损失的最常见原因， 严重的教育和语言障碍。OM的手术干预可能导致 显著的发病率，包括疼痛、面瘫、脑膜炎和脑脓肿形成。年经营 OM耗资50亿美元，对全国的医疗保健产生了巨大的影响。 虽然OM的影响是显著的，但调节这种疾病过程的细胞和分子事件 仍然知之甚少。由于只有单一的体外工具，研究受到限制 细胞培养实验本R21研究的目的是开发、表征和比较 来源于正常组织的永生化中耳（ME）上皮细胞系， 无OM病史的儿童人工耳蜗植入患者以及复发性OM（ROM）和OM患者 有积液（OME）。然后，这些细胞系将提供给OM研究界，以进一步研究 比较分析。 OM患者和对照CI队列研究的最新体外细胞系、体内动物和临床数据 受试者强烈支持MUC 5 B和miRNA-146在OM的病理生理学中的关键作用。的影响 重组TNF-α和IL-1β对MUC 5 B和miRNA 146表达水平的影响，因为它们与发病机制有关 的OM，将在这些新的细胞系中测量。 这些新工具将增强，甚至可能改变，基于狭隘的假设， 调查窗口该项目建立的细胞系将有助于OM研究社区， 了解成人和儿童患者之间的差异，并揭示潜在的机制 区分患有OM的患者和不患有OM的患者。

Project Summary Otitis media (OM) affects more than 90% of children by the age of five and is the most common indication for antimicrobial therapy in children. OM is also the most common cause of hearing loss in children and can lead to significant educational and speech delays if left untreated. Surgical interventions for OM can cause significant morbidity including pain, facial paralysis, meningitis, and brain abscess formation. With an annual cost of $5 billion, OM has a large impact on health care nation-wide. Although the impact of OM is significant, the cellular and molecular events that regulate this disease process are still poorly understood. Investigations have been limited by having only a singular tool to conduct in vitro cell culture experiments. The objective of this R21 study is to develop, characterize, and compare immortalized middle ear (ME) epithelial cell lines derived from normal tissue obtained from both adult and pediatric cochlear implant patients without a history of OM and from patients with recurrent OM (ROM) and OM with effusion (OME). These cell lines will then be made available to the OM research community for further comparative analyses. Recent in vitro cell line, in vivo animal, and clinical data from a cohort study of OM patients and control CI subjects strongly support a key role for MUC5B and miRNA-146 in the pathophysiology of OM. The effect of recombinant TNF-α and IL-1β on MUC5B and miRNA146 expression levels, as they relate to the pathogenesis of OM, will be measured in these novel cell lines. These new tools will enhance, and potentially even change, assumptions which have been based on a narrow window of investigation. The cell lines established by this project will aid the OM research community to understand the differences between adult and pediatric patients and uncover potential mechanisms differentiating patients who suffer from OM from those who do not.