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Neutrophil extracellular traps promote ?Np63+ basal cell hyperplasia in chronic rhinosinusitis

Lim, S;Khalmuratova, R;Lee, YY;Kim, YS;Lee, M;Lee, NK;Kim, SN;Choy, YB;Park, CG;Kim, DW;Shin, HW;

Neutrophil extracellular traps (NETs) are observed in chronic rhinosinusitis (CRS), although their role remains unclear.This study aimed to investigate the influence of NETs on the CRS epithelium.Forty-five sinonasal biopsy specimens were immunofluorescence-stained to identify NETs and p63+ basal stem cells. Investigators treated human nasal epithelial cells with NETs and studied them with immunofluorescence staining, Western blotting, and quantitative real-time PCR. NET inhibitors were administered to a murine neutrophilic nasal polyp model.NETs existed in tissues in patients with CRS with nasal polyps, especially in noneosinophilic nasal polyp tissues. p63+ basal cell expression had a positive correlation with the release of NETs. NETs induced the expansion of Ki-67+p63+ cells. We found that ?Np63, an isoform of p63, was mainly expressed in the nasal epithelium and controlled by NETs. Treatment with deoxyribonuclease (DNase) I or Sivelestat (NET inhibitors) prevented the overexpression of ?Np63+ epithelial stem cells and reduced polyp formation.These results reveal that NETs are implicated in CRS pathogenesis via basal cell hyperplasia. This study suggests a novel possibility of treating CRS by targeting NETs.