Tsai Yih-Jeng, Hsu Yu-Ting, Ma Ming-Chieh, Wu Chun-Kuang, Luo Sheng-Dean, Wu Wen-Bin
Department of Otolaryngology Head and Neck Surgery, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111045, Taiwan.
School of Medicine, Fu Jen Catholic University, New Taipei City 242062, Taiwan.
Antioxidants (Basel). 2022 Sep 25;11(10):1899. doi: 10.3390/antiox11101899.
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complicated inflammatory disease, and the underlying mechanism remains unclear. While some reactive oxygen/nitrogen species-related gene products are reported to participate in CRSwNP, a systemic and full analysis of oxidative-stress-associated genes in CRSwNP has not been extensively studied. Therefore, this study sought to catalog the gene-expression patterns related to oxidative stress and antioxidant defense in control and CRSwNP patients. In total, 25 control and 25 CRSwNP patients were recruited. The distribution and expression of 4-hydroxynonenal and 3-nitrotyrosine as markers of oxidative stress-which is represented by lipid peroxidation and the protein nitration of tyrosine residues in CRSwNP nasal polyps (NPs)-were more apparently increased than those found in the control nasal mucosae, as determined by immunohistochemistry (IHC). The expression of 84 oxidative-stress-related genes in nasal mucosae and NP tissues was analyzed via real-time PCR, which showed that 19 genes and 4 genes were significantly up- and downregulated, respectively; among them, inducible nitric oxide synthase (iNOS) and heme oxygenase 1 (HO-1) were notably upregulated, whereas lactoperoxidase (LPO), myeloperoxidase (MPO), and superoxide dismutase 3 (SOD3) were highly downregulated. Changes in the mRNA and protein levels of these redox proteins were confirmed with a customized, real-time PCR array and RT-PCR analysis, as well as Western blotting and IHC assays. A receiver operating characteristic curve analysis further suggested that LPO, MPO, SOD3, HO-1, and iNOS are possible endotype predictors of CRSwNP development. Collectively, we present an oxidative-stress-related gene profile of CRSwNP NP tissues, providing evidence that the systemic changes in oxidative stress and the antioxidative defense system, including novel iNOS, heme peroxidases, and other genes, are closely linked to CRSwNP pathology, development, and progression.
伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）是一种复杂的炎症性疾病，其潜在机制尚不清楚。虽然有报道称一些活性氧/氮物种相关基因产物参与了CRSwNP，但尚未对CRSwNP中氧化应激相关基因进行全面系统的分析。因此，本研究旨在梳理对照人群和CRSwNP患者中与氧化应激和抗氧化防御相关的基因表达模式。总共招募了25名对照者和25名CRSwNP患者。通过免疫组织化学（IHC）测定发现，作为氧化应激标志物的4-羟基壬烯醛和3-硝基酪氨酸在CRSwNP鼻息肉（NP）中的分布和表达——以脂质过氧化和酪氨酸残基的蛋白质硝化来表示——比对照鼻黏膜中的明显增加。通过实时PCR分析鼻黏膜和NP组织中84个氧化应激相关基因的表达，结果显示分别有19个基因显著上调和4个基因显著下调；其中，诱导型一氧化氮合酶（iNOS）和血红素加氧酶1（HO-1）显著上调，而乳过氧化物酶（LPO）、髓过氧化物酶（MPO）和超氧化物歧化酶3（SOD3）高度下调。通过定制的实时PCR阵列、RT-PCR分析以及蛋白质免疫印迹和IHC检测，证实了这些氧化还原蛋白的mRNA和蛋白质水平的变化。受试者工作特征曲线分析进一步表明，LPO、MPO、SOD3、HO-1和iNOS可能是CRSwNP发生发展的内型预测指标。总体而言，我们展示了CRSwNP鼻息肉组织中与氧化应激相关的基因谱，证明氧化应激和抗氧化防御系统的系统性变化，包括新发现的iNOS、血红素过氧化物酶和其他基因，与CRSwNP的病理、发生发展密切相关。
