NOX2 Mediates NLRP3/ROS Facilitating Nasal Mucosal Epithelial Inflammation in Chronic Rhinosinusitis with Nasal Polyps

Overview

Journal Heliyon

Specialty Social Sciences

Date 2024 Sep 27

PMID 39328569

Authors

Sijie Jiang

Benjian Zhang

Sihui Wen

Shenghao Cheng

Yingchun Shen

Shaobing Xie

Zhihai Xie

Weihong Jiang

Affiliations

Soon will be listed here.

Abstract

Background: Previous investigations have provided limited insight into the role of oxidative stress in nasal mucosa inflammation. The aim of this study was to investigate the mechanism of oxidative stress in the epithelial cells of chronic rhinosinusitis with nasal polyps CRSwNP utilizing single-cell RNA sequencing data.

Methods: Single-cell RNA sequencing data from HRA000772 were used to assess oxidative stress, inflammasome activation, and nicotinamide adenine dinucleotide phosphate oxidases (NOXs) expression in epithelial cells via integrative rank-based gene set enrichment analysis. The localization of reactive oxygen species (ROS) and NOX2 in nasal mucosa and cell models was visualized using fluorescent probes and immunohistochemistry, respectively. Functional studies on NOX2 involved siRNA and plasmid transfections , while Nucleotide-binding oligomerization domain-like receptor family pyrin domain containing 3 (NLRP3) inflammasome activity was examined using the inducer TMAO and the inhibitor MCC950.

Results: Single-cell RNA sequencing data suggested an increase of oxidative stress score and NLRP3 inflammasome score in CRSwNP epithelial cells. Vitro experiments demonstrated that lipopolysaccharide could induce ROS accumulation, NLRP3 inflammasome activation and epithelial alarmin expression. MCC950 inhibited the expression of epithelia alarmin . Elevated NOX2 in CRSwNP epithelial cells was associated with increased ROS, NLRP3 inflammasome activation, and epithelial alarmin expression. NOX2-targeted siRNA inhibited these effects . Moreover, TMAO reversed the downregulation of epithelial alarmins without impacting ROS levels.

Conclusion: This study highlights the crucial role of NOX2 as a key regulator of ROS accumulation and NLRP3 inflammasome activation in CRSwNP, underscoring its potential as a valuable therapeutic target for CRSwNP.

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