Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Department of Otolaryngology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore.
Mol Immunol. 2023 Jul;159:1-14. doi: 10.1016/j.molimm.2023.05.004. Epub 2023 May 22.
Nitric oxide (NO) is an important messenger molecule widely present in the human body. However, the role of nasal NO (nNO) in eosinophilic chronic rhinosinusitis with nasal polyps (Eos CRSwNP) remain unclear. This study aimed to investigate the diagnostic value and underlying mechanism of nNO in Eos CRSwNP.
The medical records of 84 non-Eos CRSwNP patients, 55 Eos CRSwNP patients, and 37 control subjects were retrospectively reviewed. The diagnostic value of nNO for Eos CRSwNP was assessed. The expression of inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), and tight junctions (TJs) components claudin-1, occludin, and ZO-1 was detected in the nasal polyps. Primary human nasal epithelial cells (HNECs) were co-treated with eNOS inhibitor (L-NAME) or Akt inhibitor (MK-2206), interleukin (IL)-13, and dexamethasone (Dex). The level of NO and the expression of TJs and Akt/eNOS pathways were examined.
The nNO levels of the CRSwNP group were significantly lower than those of the control group. Compared with the non-Eos CRSwNP group, the Eos CRSwNP group showed higher nNO level. The combination of nNO level, eosinophilic percentage, and posterior ethmoid score had a better predictive value for Eos CRSwNP (AUC = 0.855). The expression of iNOS, eNOS, and p-eNOS was higher in the CRSwNP groups than in the control group, and p-eNOS expression was higher in the Eos CRSwNP group than in the non-Eos CRSwNP group. The expression of TJs was lower in the Eos CRSwNP group than in the non-Eos CRSwNP and control group. IL-13 decreased TJ expression in HNECs, while Dex promoted Akt and eNOS phosphorylation, NO production and TJ expression. Furthermore, these effects of Dex were inhibited by L-NAME and MK-2206 in HNECs.
nNO may have a high diagnostic value in Eos CRSwNP, and Akt/eNOS pathway may promote the generation of NO to protect TJs. NO may have a potentially important role in the diagnosis and treatment of Eos CRSwNP.
一氧化氮（NO）是一种广泛存在于人体中的重要信使分子。然而，鼻内 NO（nNO）在嗜酸性慢性鼻-鼻窦炎伴鼻息肉（Eos CRSwNP）中的作用尚不清楚。本研究旨在探讨 nNO 在 Eos CRSwNP 中的诊断价值及其潜在机制。
回顾性分析 84 例非嗜酸性慢性鼻-鼻窦炎伴鼻息肉（non-Eos CRSwNP）患者、55 例嗜酸性慢性鼻-鼻窦炎伴鼻息肉（Eos CRSwNP）患者和 37 例对照组患者的病历资料。评估 nNO 对 Eos CRSwNP 的诊断价值。检测鼻息肉中诱导型一氧化氮合酶（iNOS）、内皮型一氧化氮合酶（eNOS）和紧密连接（TJ）成分 Claudin-1、Occludin 和 ZO-1 的表达。将原代人鼻上皮细胞（HNECs）与 eNOS 抑制剂（L-NAME）或 Akt 抑制剂（MK-2206）、白细胞介素（IL）-13 和地塞米松（Dex）共同孵育。检测 NO 水平以及 TJ 和 Akt/eNOS 通路的表达。
CRSwNP 组的 nNO 水平明显低于对照组。与 non-Eos CRSwNP 组相比，Eos CRSwNP 组的 nNO 水平更高。nNO 水平、嗜酸性粒细胞百分比和后筛评分的联合对 Eos CRSwNP 具有更好的预测价值（AUC = 0.855）。CRSwNP 组中 iNOS、eNOS 和 p-eNOS 的表达均高于对照组，Eos CRSwNP 组 p-eNOS 的表达高于 non-Eos CRSwNP 组。Eos CRSwNP 组 TJ 的表达低于 non-Eos CRSwNP 组和对照组。IL-13 降低了 HNECs 中 TJ 的表达，而 Dex 促进了 Akt 和 eNOS 的磷酸化、NO 的产生和 TJ 的表达。此外，Dex 在 HNECs 中的这些作用被 L-NAME 和 MK-2206 抑制。
nNO 对 Eos CRSwNP 可能具有较高的诊断价值，Akt/eNOS 通路可能通过促进 NO 的产生来保护 TJ。NO 可能在 Eos CRSwNP 的诊断和治疗中具有重要作用。
