Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Department of Otolaryngology, Nanning, Guangxi, China; Guangxi University of Chinese Medicine, Nanning, Guangxi, China.
Guangxi Academy of Medical Sciences, The People's Hospital of Guangxi Zhuang Autonomous Region, Department of Otolaryngology, Nanning, Guangxi, China.
Int Immunopharmacol. 2023 Mar;116:109832. doi: 10.1016/j.intimp.2023.109832. Epub 2023 Feb 8.
Although recent studies have shown that the Notch signalling pathway induces the production of Th2-related immune factors, the exact mechanism through which Notch signalling exacerbates allergic rhinitis (AR) remains unknown. To investigate the roles of Notch in AR, serum, nasal mucosa and spleen samples were isolated from BALB/c mice. Paraffin sections were stained with haematoxylin and eosin (H&E) or periodic acid-Schiff (PAS) to assess inflammation. Flow cytometry was performed to detect group 2 innate lymphoid cells (ILC2s) in the serum samples, and cytokine levels were measured by enzyme-linked immunosorbent assays (ELISAs). The mRNA expression levels of the Notch signalling pathway components and miR-155 were measured by quantitative real-time PCR (qRT-PCR). In addition, human nasal epithelial cells (HNEpCs) were cultured to investigate the functional consequences of Notch pathway inhibition. The findings demonstrated that symptomatology and pathology were substantially altered, and AR model mice were established. In vivo stimulation with ovalbumin (OVA) significantly increased the Th2-type immune responses and the expression of OVA-sIgE, IL-4, GATA3, NF-κB and miR-155. However, the Notch signalling pathway was significantly deteriorated in AR, and this effect was accompanied by reduced Notch1, Notch2, RBPj and Hes1 levels. These effects were abrogated by gamma-secretase inhibitor IX (DAPT) treatment, and DAPT inhibited the wound healing and proliferation of HNEpCs in a dose-dependent manner. Therefore, our results suggest that blocking the Notch pathway may alleviate miR-155-mediated inflammation via the regulation of immune homeostasis in AR.
尽管最近的研究表明 Notch 信号通路诱导产生了 Th2 相关免疫因子，但 Notch 信号通路加剧过敏性鼻炎（AR）的确切机制仍不清楚。为了研究 Notch 在 AR 中的作用，从 BALB/c 小鼠中分离血清、鼻黏膜和脾脏样本。用苏木精和伊红（H&E）或过碘酸希夫（PAS）染色评估炎症。通过流式细胞术检测血清样本中的 2 型固有淋巴细胞（ILC2），并通过酶联免疫吸附试验（ELISA）测量细胞因子水平。通过定量实时 PCR（qRT-PCR）测量 Notch 信号通路成分和 miR-155 的 mRNA 表达水平。此外，培养人鼻上皮细胞（HNEpCs）以研究 Notch 途径抑制的功能后果。研究结果表明，症状和病理发生了明显改变，建立了 AR 模型小鼠。卵清蛋白（OVA）体内刺激显著增加了 Th2 型免疫反应和 OVA-sIgE、IL-4、GATA3、NF-κB 和 miR-155 的表达。然而，在 AR 中 Notch 信号通路显著恶化，这种作用伴随着 Notch1、Notch2、RBPj 和 Hes1 水平的降低。DAPT（Notch 信号通路抑制剂）处理可消除这些影响，并且 DAPT 以剂量依赖性方式抑制 HNEpCs 的伤口愈合和增殖。因此，我们的结果表明，阻断 Notch 通路可能通过调节 AR 中的免疫稳态来减轻 miR-155 介导的炎症。
