NRP1 antagonism as a novel therapeutic target in nasal polyps of patients with chronic rhinosinusitis

IF 12.6 1区 医学 Q1 ALLERGY
Allergy Pub Date : 2024-08-21 DOI:10.1111/all.16285
Roza Khalmuratova, Jae-Sung Ryu, Ji Hyeon Hwang, Yi Sook Kim, Suha Lim, Ji-Hun Mo, Jong-Yeup Kim, Hyun-Woo Shin
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Abstract

Background

Neuropilin-1 (NRP1) is expressed on the surface epithelium of respiratory tract and immune cells, demonstrating its possible function in regulating the immune response in airway disease. However, its role in patient with chronic rhinosinusitis (CRS) remains unknown. This study aimed to elucidate the role of NRP1 in CRS with nasal polyps (CRSwNP).

Methods

Sinonasal biopsy specimens were immunohistochemically stained to investigate NRP1 expression. Double immunofluorescence, immunoblotting, and real-time polymerase chain reaction were performed to evaluate NRP1 in primary human nasal epithelial cells (hNECs). An NRP1 inhibitor was administered to a murine nasal polyp (NP) model.

Results

NRP1 was highly expressed in the epithelium in patients with CRSwNP compared to nasal tissue from controls and CRS without NP patients. NRP1 and vascular endothelial growth factor were upregulated in hNECs under hypoxia. Treatment with NRP1 inhibitor (EG00229) reduced the secretion of interleukin (IL)-1β, IL-6, IL-8, and IL-33 cytokines, as well as inducible nitric oxide synthase, cyclooxygenase-2, and prostaglandin E2 in hNECs. We found that NRP1 was highly expressed in the airway epithelium in the murine NP model. The group treated with the NRP1 inhibitor had significantly fewer nasal polypoid lesions and reduced accumulations of immune cells.

Conclusions

These findings reveal that NRP1 is upregulated in CRS and NP epithelium, and the inhibition of NRP1 may lead to a reduction in NP growth and immune cell infiltration. Our results suggest that NRP1 inhibition could be a novel possibility for treating nasal polyposis.

Abstract Image

将 NRP1 拮抗剂作为慢性鼻炎患者鼻息肉的新型治疗靶点。
背景:神经泌素-1(NRP1)在呼吸道上皮细胞和免疫细胞表面表达,这表明它可能具有调节气道疾病免疫反应的功能。然而,它在慢性鼻炎(CRS)患者中的作用仍然未知。本研究旨在阐明 NRP1 在伴有鼻息肉的 CRS(CRSwNP)中的作用:方法:对鼻窦活检标本进行免疫组化染色,研究 NRP1 的表达。对原代人鼻上皮细胞(hNECs)中的 NRP1 进行双重免疫荧光、免疫印迹和实时聚合酶链反应评估。在小鼠鼻息肉(NP)模型中使用了 NRP1 抑制剂:结果:与对照组和无鼻息肉 CRS 患者的鼻腔组织相比,NRP1 在 CRSwNP 患者的上皮细胞中高表达。缺氧条件下,NRP1 和血管内皮生长因子在 hNECs 中上调。用 NRP1 抑制剂(EG00229)治疗可减少 hNECs 中白细胞介素 (IL)-1β、IL-6、IL-8 和 IL-33 细胞因子以及诱导型一氧化氮合酶、环氧化酶-2 和前列腺素 E2 的分泌。我们发现,在小鼠 NP 模型中,NRP1 在气道上皮细胞中高表达。接受 NRP1 抑制剂治疗的组别鼻息肉病变明显减少,免疫细胞聚集也有所减少:这些研究结果表明,NRP1 在 CRS 和 NP 上皮中上调,抑制 NRP1 可减少 NP 生长和免疫细胞浸润。我们的研究结果表明,抑制 NRP1 可能是治疗鼻息肉病的一种新方法。
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来源期刊
Allergy
Allergy 医学-过敏
CiteScore
26.10
自引率
9.70%
发文量
393
审稿时长
2 months
期刊介绍: Allergy is an international and multidisciplinary journal that aims to advance, impact, and communicate all aspects of the discipline of Allergy/Immunology. It publishes original articles, reviews, position papers, guidelines, editorials, news and commentaries, letters to the editors, and correspondences. The journal accepts articles based on their scientific merit and quality. Allergy seeks to maintain contact between basic and clinical Allergy/Immunology and encourages contributions from contributors and readers from all countries. In addition to its publication, Allergy also provides abstracting and indexing information. Some of the databases that include Allergy abstracts are Abstracts on Hygiene & Communicable Disease, Academic Search Alumni Edition, AgBiotech News & Information, AGRICOLA Database, Biological Abstracts, PubMed Dietary Supplement Subset, and Global Health, among others.
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