Diagnostic value and underlying mechanism of nasal nitric oxide in eosinophilic chronic rhinosinusitis with nasal polyps

• Published in: Molecular immunology Vol. 159; pp. 1 - 14
• Main Authors: Tang, Binxiang, Tu, Junhao, Zhang, Meiping, Zhang, Zhiqiang, Yu, Jieqing, Shen, Li, Luo, Qing, Ye, Jing
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.07.2023
• Subjects: Eosinophils chronic rhinosinusitis with nasal polyps; Nasal nitric oxide; Nitric oxide; Tight junctions; FeNO; NO; eNOS; IL; Tight junctions; IgE; Eos; CRSwNP; Nasal nitric oxide; nNO; AUC; AR; CT; NOS; HNECs; Dex; Nitric oxide; iNOS; TJs; Eosinophils chronic rhinosinusitis with nasal polyps
• ISSN: 0161-5890; 1872-9142
• DOI: 10.1016/j.molimm.2023.05.004

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. •nNO has certain diagnostic value for Eos CRSwNP.•The expressions of eNOS and p-eNOS were increased in nasal polyps of CRSwNP patients.•Dex promotes NO production by activating the Akt/eNOS signaling pathway in HNECs.•Dex-induced NO protects TJs from damage by IL-13 in HNECs.