Quercetin alleviates the progression of chronic rhinosinusitis by affecting nasal mucosal epithelial remodeling, inflammation and Treg/Th17 imbalance.

Abstract

Nasal mucosal epithelial tissue remodeling and persist inflammation are related to the development of chronic rhinosinusitis (CRS). Quercetin possesses multiple biological properties in several inflammatory diseases. However, its roles in CRS remain unclear. In this study, serumstaphylococcus aureus enterotoxin B (SEB) increased inflammatory response in human nasal epithelial cells (hNECs), which was reversed by quercetin. Moreover, quercetin inhibited SEB-evoked epithelial-mesenchymal transition (EMT) in hNECs by increasing EMT marker E-cadherin and decreasing N-cadherin expression. Concomitantly, SEB-induced increases in transcripts and release of MMP-9 were reduced by quercetin. Mechanistically, quercetin inhibited SEB-induced activation of the TLR2-NF-kB axis in hNECs. Moreover, restoring TLR2 signaling reversed quercetin-mediated inhibition of SEB-induced inflammation, EMT and MMP-9 expression. In vivo, quercetin attenuated histopathological changes of nasal mucosal tissues in Staphylococcus aureus-constructed CRS mice. Concomitantly, quercetin alleviated inflammatory response and nasal mucosal remodeling by suppressing EMT and MMP-9 levels. Additionally, quercetin ameliorated imbalance of Treg/Th17 proportions. Notably, quercetin suppressed activation of the TLR2-NF-kB axis, while restoring this signaling reversed quercetin-mediated protection against CRS. Thus, quercetin may attenuate pathological progression of CRS by inhibiting nasal mucosal tissue remodeling, inflammation and Treg/Th17 imbalance, which may be associated with inhibition of TLR2-NF-kB axis, supporting a promising therapeutic agent for CRS.