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

一氧化氮（NO）被认为参与调节气道清除和非特异性细胞免疫在人类气道。鼻气道持续产生大量NO，人副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和鼻窦中的功能作用与转录因子的调节机制的关系。1）我们检测了正常受试者和常年性变应性鼻炎（AR）患者鼻上皮细胞中NO产生的差异，并评估一氧化氮合酶（NOS）亚型表达与疾病严重程度之间的关系。AR患者通过同时表达不同的NOS亚型，总体上产生了更高水平的NO。鼻上皮细胞具有自发或在炎性细胞因子刺激下表达iNOS蛋白的潜在能力， ...更多信息 如IFN-γ和TNF-α。此外，利用实时NO指示剂β-2 DA，提供了一种可靠的方法来可视化和定量活细胞直接产生的NO。2）我们检测了人鼻息肉中核因子-κ B（NF-κ B）的活化，并评估了活化程度与局部细胞因子基因表达之间的关系。在上皮NF-kB活化程度与IL-8、IL-16和eotaxin mRNA表达水平之间观察到显著相关性。鼻息肉上皮中NF-kB的激活通过启动相关细胞因子的转录途径负责炎性细胞，特别是嗜酸性粒细胞的募集。由于高水平的呼出NO被认为是过敏性气道炎症的潜在标志物，因此保护iNOS基因不受其不受调节的诱导对于维持鼻内环境稳定可能是重要的，并且可能提供治疗干预的工具。少

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