鼻息肉患者中骨膜蛋白表达过多与Th2反应：与哮喘的关联
Excessive periostin expression and Th2 response in patients with nasal polyps: association with asthma.
作者信息
Wei Yi, Ma Renqiang, Zhang Jia, Wu Xingmei, Yu Guodong, Hu Xianting, Li Jian, Liu Zhuofu, Ji Wendong, Li Huabin, Wen Weiping
机构信息
Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou 510080, China.
Guangzhou Key Laboratory of Otorhinolaryngology, Guangzhou 510000, China.
出版信息
J Thorac Dis. 2018 Dec;10(12):6585-6597. doi: 10.21037/jtd.2018.11.12.
BACKGROUND
Periostin has been shown to be upregulated in chronic rhinosinusitis with nasal polyps (CRSwNP), especially in the CRSwNP patients with asthma. However, the underlying mechanism that how periostin contributes to the polyp genesis remains unclear.
METHODS
In this study, we collected 63 CRSwNP patients' nasal polyps (NPs) and 25 control subjects' uncinated tissues. The expressions of periostin, thymic stromal lymphopoietin (TSLP), and other proinflammatory cytokines were examined using IHC staining, qRT-PCR, Western blot (WB), ELISA and FACS. The eosinophil infiltration, phenotype profiles and clinical characteristics of 2 NP subtypes (eosinophilic and non-eosinophilic) were evaluated. We examined the effects and mechanisms of periostin on human nasal epithelial cells cultured at air-liquid interface (ALI).
RESULTS
The expressions of periostin in NPs with asthma were higher than without asthma and the control nasal mucosa and positively associated with the TSLP (P<0.05). And the periostin levels was positively associated with the basement membrane thickness, goblet cell hyperplasia and tissue eosinophilia polyp tissues, as well as the clinical parameters (computed tomography scores, polyp size, and polyp recurrence after endoscopic surgery). In vitro experiments show that type 2 T-helper (Th2) cytokines interleukin-4 (IL-4), IL-13 and TGF-β1 stimulates epithelial cells derived from polyp tissues to produce periostin through ERK and STAT6 signal pathways (P<0.05). Autocrine or recombinant periostin activates epithelial cells to produce TSLP via NF-κB signal pathways (P<0.05). The supernatant of periostin-treated epithelial cells activates dendritic cells (DCs), which subsequently induce naïve T cells to differentiate into Th2 cells and express IL-4 and IL-13.
CONCLUSIONS
Our findings indicate periostin may play an important role in the polyp genesis, which can be considered as a therapeutic target for the management of CRSwNP.
背景
骨膜蛋白在伴鼻息肉的慢性鼻-鼻窦炎（CRSwNP）中表达上调，尤其是在合并哮喘的CRSwNP患者中。然而，骨膜蛋白促进息肉形成的潜在机制仍不清楚。
方法
在本研究中，我们收集了63例CRSwNP患者的鼻息肉（NP）和25例对照者的钩突组织。采用免疫组化染色、qRT-PCR、蛋白质免疫印迹（WB）、酶联免疫吸附测定（ELISA）和荧光激活细胞分选术（FACS）检测骨膜蛋白、胸腺基质淋巴细胞生成素（TSLP）及其他促炎细胞因子的表达。评估了2种NP亚型（嗜酸性和非嗜酸性）的嗜酸性粒细胞浸润、表型特征和临床特征。我们研究了骨膜蛋白对气液界面（ALI）培养的人鼻上皮细胞的影响及其机制。
结果
合并哮喘的NP中骨膜蛋白的表达高于未合并哮喘者及对照鼻黏膜，且与TSLP呈正相关（P<0.05）。骨膜蛋白水平与息肉组织的基底膜厚度、杯状细胞增生和组织嗜酸性粒细胞增多以及临床参数（计算机断层扫描评分、息肉大小和内镜手术后息肉复发）呈正相关。体外实验表明，2型辅助性T（Th2）细胞因子白细胞介素-4（IL-4）、IL-13和转化生长因子-β1通过ERK和STAT6信号通路刺激息肉组织来源的上皮细胞产生骨膜蛋白（P<0.05）。自分泌或重组骨膜蛋白通过NF-κB信号通路激活上皮细胞产生TSLP（P<0.05）。经骨膜蛋白处理的上皮细胞的上清液激活树突状细胞（DC），随后诱导初始T细胞分化为Th2细胞并表达IL-4和IL-13。
结论
我们的研究结果表明骨膜蛋白可能在息肉形成中起重要作用，可被视为CRSwNP治疗的一个靶点。
Zotero 插件