BackgroundNeuropilin‐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).MethodsSinonasal 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.ResultsNRP1 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.ConclusionsThese 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.

中文翻译：

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NRP1 拮抗作用作为慢性鼻-鼻窦炎患者鼻息肉的新型治疗靶点


背景神经纤毛蛋白-1 （NRP1） 在呼吸道和免疫细胞的表面上皮上表达，证明了其在调节气道疾病免疫反应中的可能功能。然而，它在慢性鼻-鼻窦炎 （CRS） 患者中的作用仍然未知。本研究旨在阐明 NRP1 在 CRS 伴鼻息肉 （CRSwNP） 中的作用。方法鼻窦活检标本免疫组化染色，检测 NRP1 表达。进行双重免疫荧光、免疫印迹和实时聚合酶链反应以评估原代人鼻上皮细胞 （hNEC） 中的 NRP1。将 NRP1 抑制剂应用于小鼠鼻息肉 （NP） 模型。结果与对照组和无 NP 患者的 CRS 患者的鼻组织相比，NRP1 在大鼠 CRSwNP 患者的上皮中高表达。缺氧下 NRP1 和血管内皮生长因子在 hNECs 中上调。NRP1 抑制剂 （EG00229） 治疗减少了 hNEC 中白细胞介素 （IL）-1β 、 IL-6 、 IL-8 和 IL-33 细胞因子的分泌，以及诱导型一氧化氮合酶、环氧合酶-2 和前列腺素 E2 的分泌。我们发现 NRP1 在小鼠 NP 模型的气道上皮中高度表达。接受 NRP1 抑制剂治疗的组鼻息肉样病变显著减少，免疫细胞积累减少。结论这些发现揭示了 NRP1 在 CRS 和 NP 上皮中上调，抑制 NRP1 可能导致 NP 生长和免疫细胞浸润减少。我们的结果表明，NRP1 抑制可能是治疗鼻息肉病的新可能性。