Neutrophil extracellular traps promote lipopolysaccharide-induced airway inflammation and mucus hypersecretion in mice
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Yong Zou1, Xi Chen2, Jian Xiao3, Dong Bo Zhou3, Xiao Xiao Lu3, Wei Li3, Bin Xie3, Xiao Kuang3 and Qiong Chen3
1Department of Emergency Medicine, Xiangya Hospital of Central South University, Changsha, China
2Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China
3Department of Geriatrics, Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, China
Qiong Chen, email: [email protected]
Keywords: neutrophil extracellular traps; lipopolysaccharide; airway inflammation; mucus hypersecretion; TLR4/NF-κB
Received: October 09, 2017 Accepted: December 01, 2017 Published: January 08, 2018
Bacterial lipopolysaccharide (LPS) contributes to airway inflammation and mucus hypersecretion in chronic airway inflammatory diseases, such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). Neutrophil extracellular traps (NETs) are extracellular meshworks composed of DNA fibers and antimicrobial proteins. Although NET formation has been detected in COPD and CF patients, how NETs contribute to these diseases is poorly understood. This study was performed to clarify the effects and mechanisms of action of NETs in airway inflammation and mucus hypersecretion. We created a murine model of LPS-induced airway inflammation and mucus hypersecretion, and found that LPS-induced NET formation was degraded by aerosolized DNase I treatment in mice. Degradation of NETs by aerosolized DNase I reduced LPS-induced airway inflammation and mucus hypersecretion in mice, this reduction correlated with suppression of TLR4/NF-κB signaling pathway. More importantly, NETs promoted LPS-induced production of IL-1β, IL-6 and TNF-α in macrophages. These results suggest NET degradation using aerosolized DNase I is a potential new therapeutic strategy for treating COPD and CF.
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