INFLAMMATORY MECHANISMS IN VIRAL OTITIS MEDIA

病毒性中耳炎的炎症机制

• 批准号: 6379202
• 负责人: Craig A. Buchman
• 金额: $ 15.22万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-07-01 至 2005-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6379202
• 关键词: clinical research; cytokine; enzyme linked immunosorbent assay; human subject; in situ hybridization; inflammation; influenzavirus A; middle ear; otitis media; polymerase chain reaction; respiratory epithelium; virus diseases; virus infection mechanism

Acute otitis media (AOM) and viral upper respiratory tract infections (URIs) represent the two most common diseases affecting the human population, and account for substantial patient morbidity and health care costs. Epidemiological and experimental studies suggest that URIs play a causal role in the pathogenesis of AOM. Specifically, viruses can invade the middle ear (ME) space and invoke an inflammatory response that culminates in ME effusion (fluid) formation and consequent symptoms (pain, hearing loss). The molecular events responsible for the inflammatory response of the human ME following viral exposure have not been characterized. Studies using viral inoculation of nasal and tracheobronchial tissues suggest that the initiating inflammatory events are epithelium-mediated through local cytokine production. Since the ME normally does not contain aggregates of leukocytes, it is likely that the initiating events in viral otitis media are epithelium-mediated as well. The long-term goal of the present study is to investigate the ME mucosal response(s) to viral exposure in an effort to better understand the initiating events in AOM. Such knowledge will help develop new therapies for this significant disease. The goals of this project are to: (1) perform influenza A viral challenge experiments in the laboratory's normal ME epithelial cell culture system and measure expression of the interleukin (IL,)-1alpha, IL-1beta, IL-6, IL-8, IL-10 and tumor necrosis factor (TNF)-alpha genes using reverse transcriptase- polymerase chain reaction (RT-PCR), in situ hybridization, and enzyme-linked immunoabsorbent assays (ELISA); (2) evaluate the same cytokine responses in ME epithelial cells derived from "otitis-prone" individuals; and (3) evaluate the efficacy of several potentially inhibitory substances in these models. The results of these experiments will provide a better understanding of the initiating events in viral otitis media and, hopefully, will lead to the development of novel therapies for this disease. Successful completion of this award by the principal investigator (PI) will provide the added research training and career development for future large-scale studies as an independent investigator.

急性中耳炎 (AOM) 和病毒性上呼吸道感染 (URI) 是影响人类的两种最常见疾病，导致大量患者发病和医疗费用。 流行病学和实验研究表明，URI 在 AOM 的发病机制中起着因果作用。具体来说，病毒可以侵入中耳 (ME) 空间并引发炎症反应，最终导致中耳积液（液体）形成和随之而来的症状（疼痛、听力损失）。 病毒暴露后导致人类 ME 炎症反应的分子事件尚未得到表征。 对鼻腔和气管支气管组织进行病毒接种的研究表明，引发的炎症事件是上皮通过局部细胞因子的产生介导的。 由于 ME 通常不包含白细胞聚集体，因此病毒性中耳炎的起始事件也可能是上皮介导的。 本研究的长期目标是调查 ME 粘膜对病毒暴露的反应，以更好地了解 AOM 的起始事件。 这些知识将有助于开发针对这种重大疾病的新疗法。 该项目的目标是：（1）在实验室正常ME上皮细胞培养系统中进行甲型流感病毒攻毒实验，并测量白细胞介素（IL，）-1α、IL-1β、IL-6、IL-8的表达使用逆转录酶聚合酶链式反应 (RT-PCR)、原位杂交和酶联免疫吸附测定 (ELISA) 检测 IL-10 和肿瘤坏死因子 (TNF)-α 基因； (2) 评估来自“易患中耳炎”个体的 ME 上皮细胞中相同的细胞因子反应； (3) 评估这些模型中几种潜在抑制物质的功效。 这些实验的结果将有助于更好地了解病毒性中耳炎的起始事件，并有望促进该疾病新疗法的开发。首席研究员（PI）成功完成该奖项将为未来作为独立研究者的大规模研究提供额外的研究培训和职业发展。