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Functional roles of nitric oxide in human nose and paranasal sinuses in relation to regulatory mechanisms by transcription factors

一氧化氮在人鼻和鼻旁窦中的功能作用与转录因子的调节机制有关

基本信息

批准号：
13671781
负责人：
TAKENO Sachio
金额：
$ 1.66万
依托单位：
HIROSHIMA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2002
项目状态：
已结题

项目摘要

Nitric oxide (NO) is believed to participate in regulation of airway clearance and nonspecific cellular immunity in human airways. A large amount of NO is continuously produced in the nasal airway, and surface epithelial cells of human paranasal sinuses seem to be the dominant source of local NO production. In the present study, we have investigated functional roles of nitric oxide in human nose and paranasal sinuses in relation to regulatory mechanisms by transcription factors.1) We examined the difference in NO production in human nasal epithelial cells between normal subjects and patients with perennial allergic rhinitis (AR), and to assess relationship between expression of nitric oxide synthase (NOS) isoforms and severity of the disease. AR patients overall produced higher levels of NO through the concomitant expression of different NOS isoforms. Nasal epithelial cells have the potential ability to express iNOS protein spontaneously or upon stimulation with inflammatory cytokines, … More such as IFN-gamma and TNF-alpha. In addition, the use of DAF-2 DA, a real-time NO indicator, provided a reliable method to visualize and quantify the direct NO production of living cells.2) We examined the activation of nuclear factor-kappa B (NF-kB), one of the most important transcription factors in various inflammatory diseases, in human nasal polyps, and assessed the relationship between the degree of activation and local cytokine gene expression. Significant correlations were observed between the degree of epithelial NF-kB activation and the levels of 1L-8, IL-16, and eotaxin mRNA expression. The activation of NF-kB in the nasal polyp epithelium is responsible for the recruitment of inflammatory cells, particularly eosinophils, through the initiation of the transcriptional pathway of the related cytokines. Because the high level of exhaled NO is considered as a potential marker of allergic airway inflammation, preserving iNOS gene from its unregulated induction may be important for maintenance of nasal homeostasis and may offer a tool of therapeutic intervention. Less

一氧化氮（NO）被认为参与气道清除和非特异性细胞免疫的调节。鼻导气管中持续产生大量NO，人鼻窦表面上皮细胞似乎是局部NO产生的主要来源。在本研究中，我们研究了一氧化氮在人鼻窦和副鼻窦中的功能作用，以及转录因子的调节机制。1)我们检测了正常人和常年性变应性鼻炎（AR）患者鼻上皮细胞NO生成的差异，并评估一氧化氮合酶（NOS）异构体的表达与疾病严重程度的关系。AR患者总体上通过同时表达不同NOS亚型而产生更高水平的NO。鼻上皮细胞具有自发或受炎性细胞因子（如ifn - γ和tnf - α）刺激表达iNOS蛋白的潜在能力。此外，使用实时NO指标DAF-2 DA，为可视化和量化活细胞直接NO生成提供了可靠的方法。2)我们检测了各种炎症疾病中最重要的转录因子之一核因子- κ B （NF-kB）在人鼻息肉中的活化程度，并评估了活化程度与局部细胞因子基因表达的关系。上皮NF-kB活化程度与1L-8、IL-16和eotaxin mRNA表达水平显著相关。鼻息肉上皮NF-kB的激活通过启动相关细胞因子的转录途径，负责炎症细胞，特别是嗜酸性粒细胞的募集。由于高水平的呼出一氧化氮被认为是过敏性气道炎症的潜在标志，因此保护一氧化氮基因免受其不受调节的诱导可能对维持鼻腔稳态很重要，并可能提供治疗干预的工具。少