Zhang Jia, Cao Yujie, Chen Kun, Hu Xianting, Zhou Chun, Li Lei, Han Miaomiao, Wang Dehui, Li Huabin
Allergy Center, Department of Otolaryngology, Affiliated Eye and ENT Hospital, Fudan University, Shanghai, China.
Department of Otolaryngology, Affiliated Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Asia Pac Allergy. 2024 Aug;14(3):97-102. doi: 10.5415/apallergy.0000000000000148. Epub 2024 Jun 17.
The importance of IL-37 and downstream signal in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP) demanding further investigation.
We sought to address the potential importance of the IL-37-IL-1R8 axis in regulating inflammatory response in patients with CRSwNP.
Nasal polyp (NP) tissues and control sinonasal tissues were obtained from adult CRSwNP, chronic rhinosinusitis without nasal polyps patients and healthy control subjects. The mRNA and protein levels of IL-37 and IL-1R8 in nasal tissues were examined by using quantitative PCR, immunohistochemical staining, and immunoblotting. In addition, the regulation of IL-1R8 expression was evaluated in human nasal epithelial cells (HNECs) in the presence of different stimuli.
The mRNA and protein levels of IL-37 and IL-1R8 were significantly elevated in nasal polyps compared with that in control tissues. IL-37 and IL-1R8 were mainly distributed in the epithelial layer and lamina propria of tissues. IL-1R8 mRNA level in nasal polys was negatively associated with eosinophil and neutrophil infiltration, as well as endoscopic score and computed tomography score. Moreover, the mRNA expression of IL-1R8 in HNECs was significantly increased by toll-like receptor agonists, but significantly inhibited by proinflammatory cytokines, which can be rescued by using steroid (DEX).
Our findings showed that enhanced IL-37-IL-1R8 axis in NP tissues was negatively associated with inflammatory and clinical severity of CRSwNP patients, which could be considered as a future therapeutic target in CRSwNP patients.
白细胞介素-37（IL-37）及其下游信号在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）发病机制中的重要性有待进一步研究。
我们试图探讨IL-37-IL-1R8轴在调节CRSwNP患者炎症反应中的潜在重要性。
从成年CRSwNP患者、不伴鼻息肉的慢性鼻-鼻窦炎患者及健康对照者获取鼻息肉（NP）组织和对照鼻窦组织。采用定量PCR、免疫组化染色和免疫印迹法检测鼻组织中IL-37和IL-1R8的mRNA和蛋白水平。此外，在不同刺激条件下评估人鼻上皮细胞（HNECs）中IL-1R8表达的调控情况。
与对照组织相比，鼻息肉中IL-37和IL-1R8的mRNA和蛋白水平显著升高。IL-37和IL-1R8主要分布于组织的上皮层和固有层。鼻息肉中IL-1R8 mRNA水平与嗜酸性粒细胞和中性粒细胞浸润以及内镜评分和计算机断层扫描评分呈负相关。此外，Toll样受体激动剂可显著增加HNECs中IL-1R8的mRNA表达，但促炎细胞因子可显著抑制其表达，而使用类固醇（地塞米松）可使其恢复。
我们的研究结果表明，NP组织中增强的IL-37-IL-1R8轴与CRSwNP患者的炎症和临床严重程度呈负相关，这可被视为CRSwNP患者未来的治疗靶点。
