Lipocalin-2 promotes neutrophilic inflammation in nasal polyps and its value as biomarker

IF 6.2 2区 医学 Q1 ALLERGY Allergology International Pub Date : 2024-01-01 DOI:10.1016/j.alit.2023.07.004
Chen Zhang , Huan Wang , Li Hu , Qianqian Zhang , Jiani Chen , Le Shi , Xiaole Song , Juan Liu , Kai Xue , Jingjing Wang , Dehui Wang , Xicai Sun
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Abstract

Background

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common chronic inflammatory disease of the nasal cavity and paranasal sinuses. The role of neutrophils in the pathogenesis of CRSwNP has attracted more attention in recent years, due to its association with more severe disease and reduced steroid responsiveness. Lipocalin-2 (LCN2) has been found to modulate neutrophils infiltration in other neutrophilic inflammation including inflammatory bowel disease, rheumatoid arthritis, and psoriasis. The aim was to evaluate the expression and regulator role of LCN2 in neutrophilic inflammation in CRSwNP, and its role as a potential biomarker predicting non-eosinophilic CRSwNP (neCRSwNP).

Methods

Bioinformatic analysis, immunostainings, real-time PCR and ELISA were used to analyze the expression and location of LCN2 in nasal tissues. The expression of proinflammatory mediators were assessed in nasal tissues and secretions. LCN2 production in human nasal epithelial cells (HNECs) and neutrophils, as well as its role in neutrophilic inflammation was evaluated by in vitro experiments.

Results

LCN2 was mainly located in neutrophils and HNECs of nasal polyps. LCN2 expression was also significantly higher in the polyp tissue and nasal secretions from patients with neCRSwNP. The LCN2 levels were positively correlated with type 3 inflammation markers, including G-CSF, IL-8, and IL-17. LCN2 expression could be upregulated by IL-17 A and TNF-α in HNECs, and LCN2 could also promote the expression of IL-8 in dispersed polyp cells and HNECs.

Conclusions

LCN2 could serve as a novel biomarker predicting patients with neCRSwNP, and the increased expression of LCN2 may participate in the pathogenesis of neCRSwNP.

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促进鼻息肉中性粒细胞炎症的脂联素-2 及其作为生物标记物的价值
背景 慢性鼻窦炎伴鼻息肉(CRSwNP)是一种常见的鼻腔和副鼻窦慢性炎症性疾病。近年来,中性粒细胞在 CRSwNP 发病机制中的作用引起了越来越多的关注,这是因为中性粒细胞与更严重的疾病和类固醇反应性降低有关。在其他中性粒细胞炎症(包括炎症性肠病、类风湿性关节炎和银屑病)中,已发现脂联素-2(LCN2)可调节中性粒细胞的浸润。本研究旨在评估 LCN2 在 CRSwNP 中嗜中性粒细胞炎症中的表达和调节作用,以及其作为预测非嗜中性粒细胞 CRSwNP(neCRSwNP)的潜在生物标志物的作用。评估了鼻腔组织和分泌物中促炎介质的表达。通过体外实验评估了 LCN2 在人鼻上皮细胞(HNECs)和中性粒细胞中的产生情况及其在中性粒细胞炎症中的作用。LCN2在鼻息肉患者的息肉组织和鼻腔分泌物中的表达也明显较高。LCN2 水平与 3 型炎症标志物(包括 G-CSF、IL-8 和 IL-17)呈正相关。结论LCN2可作为预测新CRSwNP患者的新型生物标记物,LCN2的表达增加可能参与了新CRSwNP的发病机制。
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来源期刊
Allergology International
Allergology International ALLERGY-IMMUNOLOGY
CiteScore
12.60
自引率
5.90%
发文量
96
审稿时长
29 weeks
期刊介绍: Allergology International is the official journal of the Japanese Society of Allergology and publishes original papers dealing with the etiology, diagnosis and treatment of allergic and related diseases. Papers may include the study of methods of controlling allergic reactions, human and animal models of hypersensitivity and other aspects of basic and applied clinical allergy in its broadest sense. The Journal aims to encourage the international exchange of results and encourages authors from all countries to submit papers in the following three categories: Original Articles, Review Articles, and Letters to the Editor.
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