ECRS中嗜酸性粒细胞颗粒蛋白的分析

T. Tsuda, Yohei Maeda, M. Hayama, K. Takeda, H. Inohara
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摘要

嗜酸性慢性鼻窦炎(ECRS)是慢性鼻窦炎(CRS)的一个亚型,其特征是嗜酸性鼻息肉病。由于多种类型的细胞在发病机制中起作用,因此ECRS是一种异质性疾病。识别每个细胞的功能对于治疗的个体化是很重要的。嗜酸性粒细胞是一种含有嗜酸性粒细胞颗粒蛋白(EGPs)的粒细胞。另一方面,EGPs具有抗寄生虫活性,由于其细胞毒性,与变应性炎症密切相关。嗜酸性粒细胞衍生神经毒素(EDN)是一种嗜酸性粒细胞颗粒蛋白。在本研究中,我们评估了EDN在ECRS发病机制中的作用。ECRS患者血清EDN水平明显高于其他鼻部和副鼻部疾病患者,且与临床疾病活动性呈正相关。EDN在ECRS鼻息肉嗜酸性粒细胞中的表达。用EDN刺激人鼻上皮细胞(HNEpCs),通过RNA测序检测其基因表达变化。通路分析显示受EDN刺激影响的主要典型通路是“上皮-间质转化(EMT)通路的调控”;该通路中唯一上调的基因是基质金属蛋白酶9 (MMP-9)。EDN可能参与ECRS的发病机制,也是一个重要的治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Analysis of eosinophil granule proteins in ECRS
Eosinophilic chronic rhinosinusitis (ECRS) is a subtype of chronic rhinosinusitis (CRS) that is characterized by eosinophilic nasal polyposis. Because several types of cells play a role in pathogenesis, ECRS is a heterogenous disease. To identify each cell function is important for the individualization of therapy. The eosinophil is a granulocyte that contain eosinophil granule proteins (EGPs). EGPs have antiparasitic activity, on the other hand, closely related allergic inflammation due to its cytotoxicity. Eosinophil-derived neurotoxin (EDN) is one of the eosinophil granule proteins. In this study, we evaluated the function of EDN in ECRS pathogenesis. Serum EDN levels were significantly higher in patients with ECRS than in those with other nasal and paranasal diseases and were positively correlated with clinical disease activity. EDN expressed in the eosinophils of ECRS nasal polyps. Human nasal epithelial cells (HNEpCs) were stimulated with EDN, and the resultant changes in gene expression were detected by RNA sequencing. Pathway analysis revealed that the major canonical pathway affected by EDN stimulation was “regulation of the epithelial–mesenchymal transition (EMT) pathway”; the only gene in this pathway to be up-regulated was matrix metalloproteinase 9 (MMP-9). EDN may be involved in the pathogenesis of ECRS and also be an important therapeutic target.
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