NOTCH-1 activation sustains hyperexpression of IL-33 in the epithelium of nasal polyps

Alterations in nasal epithelial barrier function and homeostasis may contribute to the pathogenesis of chronic rhino-sinusitis with nasal polyps (CRSwNP). The present study aimed to assess the expression of NOTCH-1 and IL-33 in the epithelium of nasal polyps recovered from allergic (n,7) and not allergic (n,7) subjects with CRSwNP by immunohistochemistry. We found that nuclear and cytoplasmic IL-33 and NOTCH-1 were expressed with a significant higher percentage of positivity in hyperplastic epithelium of allergic polyps than in hyperplastic epithelium of not allergic polyps from ex-smokers. Nuclear and cytoplasmic IL-33 and NOTCH-1 were expressed with a significant higher percentage of positivity in normal and in metaplastic epithelium of not allergic polyps from ex-smokers than in normal and metaplastic epithelium of allergic polyps. No differences were observed in the expression of both nuclear and cytoplasmic IL-33 and NOTCH-1 in basal epithelial cells. The expression of nuclear and cytoplasmic NOTCH-1 significantly and highly correlated with the expression of nuclear and cytoplasmic IL-33. In addition we demonstrated, in vitro, using flow-cytometry, immunofluorescence and immunocytochemistry, in a model of nasal epithelial cells, that the stimulation of NOTCH-1 with its agonist jagged-1 induced the nuclear and the cytoplasmic expression of IL-33. The inhibitor of NOTCH-1, DAPT did not induce IL-33 expression and reduced the effect of Jagged-1 on IL-33. In conclusion, data herein provided support, for the first time, a putative role of NOTCH-1/IL-33 axis in the differentiation abnormalities of the epithelium in patients suffering of CRSwNP.