Pathogenesis of Otitis Media with Effusion

渗出性中耳炎的发病机制

• 批准号: 7576744
• 负责人: Patricia A Hebda
• 金额: $ 27.77万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7576744
• 关键词: Acute; Animal Model; Animals; Apoptosis; Bacterial Infections; Biochemical; Biological; Biological Assay; Biological Models; Blood Vessels; Cell Communication; Cell Culture Techniques; Cells; Child; Childhood; Clinical; Collagen; Complex; Culture Media; Development; Disease; Disease model; Drug usage; Edema; Epithelial Cells; Etiology; Eustachian Tube; Fibroblasts; Future; Gap Junctions; Gases; Growth Factor; Healed; Hypoxia; Immune response; Immune system; In Vitro; Individual; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Intervention; Intervention Trial; Ion Channel; Laboratories; Lamina Propria; Lead; Lymphoid Tissue; Measures; Mediating; Medical; Metabolism; Methods; Mitosis; Mitotic; Modeling; Morphology; Mucositis; Mucous Membrane; Obstruction; Otitis Media; Otitis Media with Effusion; Pathogenesis; Pathway interactions; Permeability; Physiological; Physiology; Process; Production; Proteins; Rattus; Research Personnel; Rodent Model; Role; Signal Pathway; Signal Transduction; Signaling Molecule; Signs and Symptoms; Stimulus; Testing; Therapeutic Intervention; Tissues; Transgenic Animals; Wound Healing; age group; cell type; chemokine; cytokine; effusion; genetic manipulation; healing; inhibitor/antagonist; mRNA Expression; middle ear; migration; pressure; programs; research study; response; tissue culture

Otitis media (OM) is a common disease of the pediatric age group considered to be multifactorial in etiology. While most cases of symptomatic OM with acute onset resolve within one month of presentation, a significant percentage persists for months to years as OM with effusion (OME), and many children present with OME evidenced by middle ear (ME) mucosal inflammation and effusion without recent signs and symptoms. OME is a persistent inflammation that most often fails to respond to conventional medical therapies. Recent studies conducted by us show that hydrops ex vacuo is a valid explanation for the development and persistence of OME under certain conditions. Disrupting Eustachian tube (ET) function in animals causes middle ear (ME) pressure dysregulation reflected as underpressures, which in turn causes increased permeability of the mucosal vasculature and results in ME effusion. However, the mechanism(s) responsible for transducing the biological signals associated with the underpressure that result in ME mucosal inflammation are not known. We hypothesize that transduction of the signal associated with middle ear underpressure initiates and sustains an inflammatory process that contributes to persistence of OME and to adverse changes in ME physiology. Three Specific Aims are proposed to test this hypothesis: 1) To determine the role of inflammatory signaling in the production and persistence of ME effusion after ET obstruction, 2) To utilize tissue culture model systems for the elucidation of specific cellular mechanisms involved in disease pathogenesis, and 3) To use biochemical, pharmacologic and genetic manipulation to assess the role of key inflammatory mediators and pathways in provoking or sustaining the mucosal changes induced in the animal OME model systems. To achieve these aims, experiments are proposed using rodent models of OME and tissue cultures of ME epithelial cells and fibroblasts already established by the investigators. With these studies the investigators hope to elucidate the role of specific inflammatory signals and pathways in promoting disease persistence, and thus to identify potential targets for future therapeutic interventions.

中耳炎（OM）是儿童年龄组的一种常见疾病，被认为是多因素的