1. Blocking Notch signalling reverses miR-155-mediated inflammation in allergic rhinitis.
- Author
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Zhong, Ziling, Huang, Xueying, Zhang, Shaojie, Zheng, Shaochuan, Cheng, Xiqiao, Li, Rongrong, Wu, Di, Mo, Liping, and Qu, Shenhong
- Subjects
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NASAL mucosa , *ALLERGIC rhinitis , *NOTCH signaling pathway , *INNATE lymphoid cells , *ENZYME-linked immunosorbent assay , *AUTOREGRESSIVE models , *HOMEOSTASIS , *WOUND healing - Abstract
• DAPT treatment reverses miR-155-mediated inflammation in allergic rhinitis mice. • Notch signalling pathway was destroied in injured nasal mucosa epithelium. • DAPT has a negative regulatory effect on human nasal mucosal epithelial cells. 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. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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