Notch‐1 signaling activation sustains overexpression of interleukin 33 in the epithelium of nasal polyps
Journal of Cellular Physiology
Published online on September 27, 2018
Abstract
---
- "\nAbstract\n\nBackground\nAlterations in the nasal epithelial barrier homeostasis
and increased interleukin 33 (IL‐33) expression contribute to the pathogenesis of
chronic rhinosinusitis with nasal polyps (CRSwNP).\n\n\nAims\nAs 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;
\nn = 9) and not allergic (NA‐CRSwNP; \nn = 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).\n\n\nResults\nEx 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.\n\n\nConclusions\nThe 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.\n"
- Journal of Cellular Physiology, EarlyView.