Department of Respiratory Medicine, Ruijin Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Chin Med J (Engl). 2009 Nov 5;122(21):2647-51.
The immunologic response to allergens mediated by T lymphocytes is an incipient key element in the pathogenesis of asthma, and Th1/Th2 balance is regarded as the core of asthma pathogenesis. Notch is a single-pass transmembrane receptor protein that regulates differentiation, proliferation and apoptosis in a broad range of cells. It is considered that the Notch signal pathway works in every stage of T cell development and differentiation. Whether the pathway of asthma pathogenesis is related to Notch1 remains unknown. This study is aimed to investigate whether the pathway of asthma pathogenesis is related to Notch1 by examining the effect of knockdown of the Notch1 gene by small interfering RNA on T cell differentiation.
An OVA-induced asthma mouse model was established. The expression of Notch1 in the tissue and T cells of the lung from asthmatic mice was detected by RT-PCR and Western blotting. The expression of Notch1 and cytokine interleukin (IL)-4 and interferon (IFN)-gamma in activated lung T cells was detected by RT-PCR and enzyme-linked immunosorbent assay after blocking Notch1 by small interfering RNA.
The mRNA and protein expression of Notch1 increased significantly both in the lung tissue and lung T cells of asthmatic mice (both P < 0.05). IL-4 decreased and IFN-gamma increased significantly in active lung T cells after Notch1 was blocked by Notch1-specific small interfering RNA (IL-4: (2.51 +/- 0.51) pg/ml vs 0.64 +/- 0.27) pg/ml protein; IFN-gamma: (21.72 +/- 4.24) pg/ml vs (39.79 +/- 4.09) pg/ml protein, P < 0.05).
This study demonstrated that the Notch1 signal might play a role in the pathogenesis of asthma by its involvement in Th1/Th2 differentiation.
T 淋巴细胞介导的过敏原免疫反应是哮喘发病机制的初始关键因素，而 Th1/Th2 平衡被认为是哮喘发病机制的核心。Notch 是一种单次跨膜受体蛋白，可调节多种细胞的分化、增殖和凋亡。人们认为 Notch 信号通路在 T 细胞发育和分化的各个阶段都起作用。哮喘发病机制的途径是否与 Notch1 有关尚不清楚。本研究旨在通过检查 Notch1 基因小干扰 RNA 敲低对 T 细胞分化的影响，来研究哮喘发病机制途径是否与 Notch1 有关。
建立 OVA 诱导的哮喘小鼠模型。通过 RT-PCR 和 Western blot 检测哮喘小鼠肺组织和 T 细胞中 Notch1 的表达。用小干扰 RNA 阻断 Notch1 后，通过 RT-PCR 和酶联免疫吸附试验检测活化的肺 T 细胞中 Notch1 和细胞因子白细胞介素 (IL)-4 和干扰素 (IFN)-γ的表达。
哮喘小鼠肺组织和肺 T 细胞中 Notch1 的 mRNA 和蛋白表达均显著增加（均 P < 0.05）。Notch1 特异性小干扰 RNA 阻断 Notch1 后，活化的肺 T 细胞中 IL-4 显著减少，IFN-γ 显著增加（IL-4：（2.51 +/- 0.51）pg/ml 比 0.64 +/- 0.27）pg/ml 蛋白；IFN-γ：（21.72 +/- 4.24）pg/ml 比（39.79 +/- 4.09）pg/ml 蛋白，P < 0.05）。
本研究表明，Notch1 信号可能通过参与 Th1/Th2 分化在哮喘发病机制中发挥作用。
