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

Binxiang Tang; Junhao Tu; Meiping Zhang; Zhiqiang Zhang; Jieqing Yu; Li Shen; Qing Luo; Jing Ye

doi:10.1016/j.molimm.2023.05.004

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

Mol Immunol. 2023 Jul:159:1-14. doi: 10.1016/j.molimm.2023.05.004. Epub 2023 May 22.

Authors

Binxiang Tang¹, Junhao Tu², Meiping Zhang¹, Zhiqiang Zhang¹, Jieqing Yu³, Li Shen¹, Qing Luo¹, Jing Ye⁴

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.
² 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.
³ Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Suegery, Nanchang, Jiangxi Province, China.
⁴ Department of Otorhinolaryngology, Head and Neck Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China; Institute of Jiangxi Otorhinolaryngology Head & Neck Suegery, Nanchang, Jiangxi Province, China. Electronic address: yjholly@ncu.edu.cn.

PMID: 37224640
DOI: 10.1016/j.molimm.2023.05.004

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Eosinophils chronic rhinosinusitis with nasal polyps; Nasal nitric oxide; Nitric oxide; Tight junctions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chronic Disease
Humans
Interleukin-13
NG-Nitroarginine Methyl Ester
Nasal Mucosa / metabolism
Nasal Polyps* / pathology
Nitric Oxide
Proto-Oncogene Proteins c-akt
Retrospective Studies
Rhinitis* / diagnosis
Rhinitis* / metabolism
Rhinitis* / pathology
Sinusitis* / pathology

Substances

Nitric Oxide
NG-Nitroarginine Methyl Ester
Proto-Oncogene Proteins c-akt
Interleukin-13