Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps

Salvatore Gallina, Riccardo Speciale, Di Vincenzo, Mark Gjomarkaj, Caterina Di Sano, D’Anna, Serafina Sciarrino, Giuseppina Chiappara, Elisabetta Pace, Bruno, Andreina Bruno, Francesco Lorusso

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Abstract

Background: Alterations in the nasal epithelial barrier homeostasis and increased interleukin 33 (IL-33) expression contribute to the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP). Aims: As Notch-1 signaling is crucial in repair processes of mucosa, the current study assessed Notch-1/Jagged-1 signaling and IL-33 in the epithelium of nasal polyps biopsies from allergic (A-CRSwNP; n = 9) and not allergic (NA-CRSwNP; n = 9) subjects by immunohistochemistry. We also assessed, in a model of nasal epithelial cells, the effects of stimulation of Notch-1 with Jagged-1 on the expression of IL-33 (by flow cytometry, immunofluorescence, and immunocytochemistry), Jagged-1 (by flow cytometry), and p-CREB transcription factor (by western blot analysis). Results: Ex vivo (a) in normal epithelium, the expression of Notch-1 and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (b) in metaplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in NA-CRSwNP than in A-CRSwNP; (c) in hyperplastic epithelium, the expression of Notch-1, Jagged-1, and IL-33 were higher in A-CRSwNP than in NA-CRSwNP; and (d) in basal epithelial cells, no differences were observed in the expression of Jagged-1, IL-33, and Notch-1. The expression of Notch-1 significantly correlated with the expression of IL-33. In vitro, stimulation of Notch-1 with Jagged-1 induced the expression of (a) Jagged-1; (b) IL-33; and (c) p-CREB transcription factor. The inhibitor of Notch-1, DAPT, reduced all the effects of Jagged-1 on nasal epithelial cells. Conclusions: The data herein provided support, for the first time, a putative role of Notch-1/Jagged-1 signaling in the overexpression of IL-33 in the epithelium of nasal polyps from patients with CRSwNP.
Lingua originaleEnglish
pagine (da-a)4582-4596
Numero di pagine15
RivistaJournal of Cellular Physiology
Volume234
Stato di pubblicazionePublished - 2019

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All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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Gallina, S., Speciale, R., Di Vincenzo, Gjomarkaj, M., Di Sano, C., D’Anna, Sciarrino, S., Chiappara, G., Pace, E., Bruno, Bruno, A., & Lorusso, F. (2019). Notch-1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps. Journal of Cellular Physiology, 234, 4582-4596.