Regulation of Airway Epithelial Responses in Asthma

哮喘气道上皮反应的调节

• 批准号: 6999050
• 负责人: KARIN A PROVOST
• 金额: $ 5.54万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-15 至 2007-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6999050
• 关键词: JAK kinase; asthma; biological signal transduction; cell surface receptors; cytokine receptors; enzyme activity; genetically modified animals; helper T lymphocyte; hydrolase; immunoregulation; inflammation; interferon gamma; interleukin 13; interleukin 3; interleukin 4; laboratory mouse; lung lavage; mucus; phosphorylation; postdoctoral investigator; receptor expression; respiratory epithelium; respiratory hypersensitivity

DESCRIPTION (provided by applicant): Allergic airway inflammation is a Th2 driven inflammatory process characterized by excess mucus production, eosinophilia, and airway hyperresponsiveness (AHR). Recent studies have identified that Interferon gamma (IFN-g) plays a critical role in regulating asthmatic response to inhaled allergen by reducing the Th2 effector functions noted above. It also controls airway chitinase activity, a recently characterized pro-inflammatory Th2 effector pathway in asthma. We hope to define the mechanisms by which IFN-g regulates Th2 effector function. In Aim I, we will determine how airway epithelial cells respond to IFN-g to limit Th2 responses, specifically mucus and chitinase activity. In Aim II, we will define the mechanisms by which IFN-g exerts its effects on the Th2 effector cells; acting to increase soluble immunomodulating factors such as IL-13Ra2, decreasing cell surface receptor expression or by affecting post receptor signaling cascades.

描述（由申请人提供）：过敏性气道炎症是TH2驱动的炎症过程，其特征是粘液产生过多，嗜酸性粒细胞和气道高反应性（AHR）。最近的研究表明，干扰素γ（IFN-G）通过降低上述TH2效应子函数来调节对吸入过敏原的哮喘反应起着关键作用。它还控制气道几丁质酶活性，这是最近在哮喘中表征的促炎性Th2效应途径。我们希望定义IFN-G调节Th2效应函数的机制。在目标I中，我们将确定气道上皮细胞如何响应IFN-G以限制Th2反应，特别是粘液和几丁质酶活性。在AIM II中，我们将定义IFN-G对Th2效应细胞发挥作用的机制。采取行动增加可溶性免疫调节因子，例如IL-13RA2，降低细胞表面受体表达或通过影响后受体信号级联反应。