Department of Otolaryngology Head and Neck Surgery, Xiangya Hospital of Central South University, Changsha, Hunan, China.
Province Key Laboratory of Otolaryngology Critical Diseases, Changsha, Hunan, China.
Biosci Rep. 2020 Feb 28;40(2). doi: 10.1042/BSR20193101.
Chronic rhinosinusitis with nasal polyposis (CRSwNP) represents a heterogeneous disorder that can be classified into either eosinophilic or noneosinophilic endotypes. However, the immunological mechanisms of each remain unclear. The purpose of the present study was to compare and analyze inflammatory signatures of eosinophilic CRSwNP (ECRSwNP) and noneosinophilic CRSwNP (NECRSwNP). Cytokine antibody array was used to identify inflammatory mediators that were differentially expressed among ECRSwNP, NECRSwNP, and control groups. Then, bioinformatics approaches were conducted to explore biological functions and signaling pathways. In addition, pairwise correlation analyses were performed among differential levels of inflammatory mediators and tissue eosinophil infiltration. The results showed that nine mediators were significantly up-regulated in ECRSwNP, including eotaxin-2, eotaxin-3, CCL18, IL-4, IL-5, IL-10, IL-12p70, IL-13, and IL-15. Bioinformatics analysis indicated that these mediators were mainly enriched in leukocyte chemotaxis and proliferation, JAK-STAT cascade, asthma, and Th1 and Th2 cell differentiation. Furthermore, seven mediators were identified to be significantly up-regulated in NECRSwNP, including CCL20, resistin, transforming growth factor (TGF)-β2, triggering receptor expressed on myeloid cells 1 (TREM-1), CD14, glucocorticoid-induced tumor necrosis factor receptor related protein (GITR), and lipocalin-2. These mediators were closely associated with LPS responses, neutrophil chemotaxis and migration, and IL-17 signaling pathway. In addition, pairwise correlation analyses indicated that differential levels of inflammatory mediators in ECRSwNP and NECRSwNP were broadly correlated with each other and with tissue eosinophil infiltration. In conclusion, we found that ECRSwNP and NECRSwNP exhibited different patterns of inflammatory signatures. These findings may provide further insights into heterogeneity of CRSwNP.
伴有鼻息肉的慢性鼻-鼻窦炎（CRSwNP）代表一种异质性疾病，可分为嗜酸性或非嗜酸性表型。然而，每种表型的免疫机制仍不清楚。本研究旨在比较和分析嗜酸性 CRSwNP（ECRSwNP）和非嗜酸性 CRSwNP（NECRSwNP）的炎症特征。采用细胞因子抗体芯片鉴定 ECRSwNP、NECRSwNP 和对照组之间差异表达的炎症介质。然后，通过生物信息学方法探讨生物学功能和信号通路。此外，还进行了差异炎症介质水平与组织嗜酸性粒细胞浸润之间的两两相关分析。结果显示，ECRSwNP 中有 9 种介质显著上调，包括嗜酸粒细胞趋化因子-2、嗜酸粒细胞趋化因子-3、CCL18、IL-4、IL-5、IL-10、IL-12p70、IL-13 和 IL-15。生物信息学分析表明，这些介质主要富集于白细胞趋化和增殖、JAK-STAT 级联、哮喘以及 Th1 和 Th2 细胞分化。此外，还发现 7 种介质在 NECRSwNP 中显著上调，包括 CCL20、抵抗素、转化生长因子（TGF）-β2、髓样细胞触发受体 1（TREM-1）、CD14、糖皮质激素诱导的肿瘤坏死因子受体相关蛋白（GITR）和脂钙蛋白-2。这些介质与 LPS 反应、中性粒细胞趋化和迁移以及 IL-17 信号通路密切相关。此外，两两相关分析表明，ECRSwNP 和 NECRSwNP 中差异炎症介质的水平与彼此之间以及与组织嗜酸性粒细胞浸润广泛相关。总之，我们发现 ECRSwNP 和 NECRSwNP 表现出不同的炎症特征模式。这些发现可能为 CRSwNP 的异质性提供进一步的见解。
