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

一氧化氮(NO)被认为参与了人类呼吸道清除和非特异性细胞免疫的调节。鼻腔内持续产生大量的NO，人副鼻窦表面上皮细胞似乎是局部产生NO的主要来源。1)我们检测了正常人和常年性变应性鼻炎(AR)患者鼻上皮细胞中NO产生的差异，并探讨了一氧化氮合酶(NOS)亚型的表达与疾病严重程度的关系。AR患者通过同时表达不同的一氧化氮合酶亚型产生更高水平的NO。鼻上皮细胞具有自发或在炎性细胞因子…刺激下表达诱导型一氧化氮合酶的潜在能力更多的如干扰素-γ和肿瘤坏死因子-α。此外，DAF-2 DA的使用，一个实时的NO指示剂，提供了一个可靠的方法来可视化和定量活细胞产生的直接NO。2)我们检测了核因子-kB(核因子-kB)在各种炎症性疾病中的激活情况，并评估了其激活程度与局部细胞因子基因表达的关系。1L-8、IL-16和嗜酸性粒细胞趋化素mRNA表达水平与上皮细胞核因子-kB的活化程度呈显著正相关。鼻息肉上皮中核因子-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。由于呼出的高水平的NO被认为是过敏性气道炎症的潜在标志，因此保存iNOS基因的非调控诱导对于维持鼻腔内环境的稳定可能是重要的，并可能提供一种治疗干预的工具。较少

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