Department of Otorhinolaryngology, Head and Neck Surgery, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.
Int J Mol Sci. 2021 Jul 15;22(14):7561. doi: 10.3390/ijms22147561.
The human paranasal sinuses are the major source of intrinsic nitric oxide (NO) production in the human airway. NO plays several roles in the maintenance of physiological homeostasis and the regulation of airway inflammation through the expression of three NO synthase (NOS) isoforms. Measuring NO levels can contribute to the diagnosis and assessment of allergic rhinitis (AR) and chronic rhinosinusitis (CRS). In symptomatic AR patients, pro-inflammatory cytokines upregulate the expression of inducible NOS (iNOS) in the inferior turbinate. Excessive amounts of NO cause oxidative damage to cellular components, leading to the deposition of cytotoxic substances. CRS phenotype and endotype classifications have provided insights into modern treatment strategies. Analyses of the production of sinus NO and its metabolites revealed pathobiological diversity that can be exploited for useful biomarkers. Measuring nasal NO based on different NOS activities is a potent tool for specific interventions targeting molecular pathways underlying CRS endotype-specific inflammation. We provide a comprehensive review of the functional diversity of NOS isoforms in the human sinonasal system in relation to these two major nasal disorders' pathologies. The regulatory mechanisms of NOS expression associated with the substrate bioavailability indicate the involvement of both type 1 and type 2 immune responses.
人类鼻窦是人类气道中内在一氧化氮（NO）产生的主要来源。NO 通过三种一氧化氮合酶（NOS）同工型的表达，在维持生理稳态和调节气道炎症方面发挥多种作用。测量 NO 水平有助于过敏性鼻炎（AR）和慢性鼻-鼻窦炎（CRS）的诊断和评估。在有症状的 AR 患者中，促炎细胞因子在上鼻甲中上调诱导型 NOS（iNOS）的表达。过量的 NO 会对细胞成分造成氧化损伤，导致细胞毒性物质的沉积。CRS 表型和内型分类为现代治疗策略提供了深入了解。对鼻窦 NO 及其代谢物的产生进行分析，揭示了可以利用其作为有用生物标志物的病理生物学多样性。基于不同 NOS 活性测量鼻 NO 是针对 CRS 内型特异性炎症潜在分子途径的特定干预措施的有效工具。我们全面回顾了人类鼻-鼻窦系统中 NOS 同工型的功能多样性与这两种主要鼻部疾病病理的关系。与底物生物利用度相关的 NOS 表达的调节机制表明，1 型和 2 型免疫反应均参与其中。
