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TSLP 调控嗜酸性粒细胞性 CRSwNP 患者鼻上皮细胞的 eotaxin-1 产生。

TSLP regulates eotaxin-1 production by nasal epithelial cells from patients with eosinophilic CRSwNP.

机构信息

Schools of Medicine and Nursing Sciences, Huzhou University Location: No.759, Huzhou City, Zhejiang Prov, China.

Fujian Medical University, Location: No.88, Jiaotong Road, Fuzhou City, Fujian Prov, China.

出版信息

Rhinology. 2018 Dec 1;56(4):370-377. doi: 10.4193/Rhin17.045.

Abstract

BACKGROUND

Eosinophilic chronic rhinosinusitis with nasal polyps (eCRSwNP) is characterized by Th2-skewed inflammation with eosinophilic infiltration. Thymic stromal lymphopoietin (TSLP) promotes the development of allergic inflammation. Although increased TSLP is found in eCRSwNP, little is known about whether TSLP regulates eotaxin-1 production, a potent eosinophil chemoattractant that recruits and activates eosinophils.

OBJECTIVE

The aim of this study was to investigate the effects and mechanisms of TSLP in eotaxin-1 production in the eosinophilic inflammation of eCRSwNP.

METHODS

Human nasal epithelial cells (HNECs) from eCRSwNP patients were stimulated with recombinant human TSLP in the presence or absence of CYT387 (Janus kinase 1/2 inhibitor). Phosphorylated signal transducer activator of transcription 3 (p-STAT3) was measured by using immunocytochemistry. Eotaxin-1 expression was determined by using real-time PCR. Western blotting was used to detect the levels of p-STAT3 and eotaxin-1 protein.

RESULTS

The treatment with TSLP induced STAT3 phosphorylation in HNECs, and promoted p-STAT3 nuclear translocation, leading to a time-dependent increase of eotaxin-1 expression. However, these effects were attenuated by CYT387 pretreatment.

CONCLUSION

TSLP regulated eotaxin-1 production in HNECs via JAK1/2-STAT3 signaling, which might contribute to the eosinophilic inflammation of eCRSwNP.

摘要

背景

伴有鼻息肉的嗜酸性慢性鼻-鼻窦炎(eCRSwNP)的特征是 Th2 偏向炎症伴嗜酸性浸润。胸腺基质淋巴细胞生成素(TSLP)促进过敏炎症的发展。虽然在 eCRSwNP 中发现 TSLP 增加,但尚不清楚 TSLP 是否调节嗜酸性粒细胞趋化因子-1(一种有效的嗜酸性粒细胞趋化因子,可募集并激活嗜酸性粒细胞)的产生。

目的

本研究旨在探讨 TSLP 在 eCRSwNP 嗜酸性粒细胞炎症中诱导 eotaxin-1 产生的作用及其机制。

方法

用重组人 TSLP 刺激 eCRSwNP 患者的人鼻上皮细胞(HNECs),并在存在或不存在 CYT387(Janus 激酶 1/2 抑制剂)的情况下进行刺激。通过免疫细胞化学测定磷酸化信号转导子和转录激活子 3(p-STAT3)。通过实时 PCR 测定 eotaxin-1 的表达。用 Western blot 检测 p-STAT3 和 eotaxin-1 蛋白的水平。

结果

TSLP 处理诱导 HNECs 中 STAT3 磷酸化,并促进 p-STAT3 核转位,导致 eotaxin-1 表达呈时间依赖性增加。然而,这些作用被 CYT387 预处理所减弱。

结论

TSLP 通过 JAK1/2-STAT3 信号通路调节 HNECs 中的 eotaxin-1 产生,这可能有助于 eCRSwNP 的嗜酸性粒细胞炎症。

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