Wogonin attenuates nasal polyp formation by inducing eosinophil apoptosis through HIF-1\u03b1 and survivin suppression

Roza Khalmuratova,Jong-Wan Park,Mingyu Lee,Yunjae Jung,Ji-Hun Mo,Hyun-Woo Shin

doi:10.1038/s41598-018-24356-5

Abstract

Chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) is an inflammatory sinonasal disorder characterized by eosinophilic inflammation and T-helper 2 skewing. Eosinophil accumulation in sinonasal mucosa comprises a major feature of CRSwNP. The study aimed to investigate the effect of the flavone wogonin in nasal polyposis by assessing its ability to induce eosinophil apoptosis in vitro and attenuate eosinophilic CRSwNP in mice. Double immunofluorescence, immunohistochemistry, flow cytometry, and immunoblotting were performed to evaluate hypoxia-inducible factor (HIF)-1α, survivin, and apoptotic markers in the human eosinophilic EoL-1 cell line or sinonasal tissues from patients with CRS with or without NPs. In sinonasal specimens from patients with CRS, HIF-1α and survivin were up-regulated in eosinophils from patients with NPs compared with levels in patients without NPs. Under hypoxia, HIF-1α and survivin expression was up-regulated in EoL-1 cells. Wogonin down-regulated both HIF-1α and survivin in EoL-1 cells. In addition, overexpression of survivin protected EoL-1 cells against apoptosis in response to wogonin. Moreover, wogonin attenuated nasal polyp formation in a murine model. Our findings suggest that wogonin could induce caspase-3 activation by suppressing HIF-1α and survivin expression in EoL-1 cells. Further studies regarding novel therapeutic options for CRSwNP targeting eosinophil apoptosis are needed.

Highlights

Chronic rhinosinusitis (CRS) is a highly prevalent and heterogeneous disorder, characterized by chronic inflammation of the nasal cavity and paranasal sinus mucosa
We aimed to investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate nasal polyp formation in a mouse model of CRS exposed to ovalbumin (OVA)/Staphylococcal enterotoxin B (SEB)
Tissue samples were collected from patients with CRS with (CRSwNP) and without (CRSsNP) (UP tissues), patients with CRSwNP (NP and uncinate process (UP) tissues), and healthy subjects (UP tissues) to evaluate hypoxia-inducible factor (HIF)-1α expression levels (Table 1)

Summary

Introduction

Chronic rhinosinusitis (CRS) is a highly prevalent and heterogeneous disorder, characterized by chronic inflammation of the nasal cavity and paranasal sinus mucosa. Increasing evidence suggest that eosinophilic inflammation is correlated with polyp recurrence[6,7]. These findings support a role for eosinophils in CRSwNP, the pathophysiology of this disease remains incompletely understood. The combined hypoxia and allergen enhanced HIF-1α expression and increased eotaxin-1, peribronchial eosinophils, and degree of airway remodeling (fibrosis) compared to either stimulus alone. These findings indicate that hypoxia may cause a profound effect on eosinophil function. We aimed to investigate the ability of the flavone wogonin to induce eosinophil apoptosis in vitro and attenuate nasal polyp formation in a mouse model of CRS exposed to ovalbumin (OVA)/Staphylococcal enterotoxin B (SEB)

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