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.
Rhinology. 2018 Dec 1;56(4):370-377. doi: 10.4193/Rhin17.045.
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.
The aim of this study was to investigate the effects and mechanisms of TSLP in eotaxin-1 production in the eosinophilic inflammation of eCRSwNP.
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.
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.
TSLP regulated eotaxin-1 production in HNECs via JAK1/2-STAT3 signaling, which might contribute to the eosinophilic inflammation of eCRSwNP.
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。
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。
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。
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。
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。