Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice

The pathogenesis of acute lung injury is complex. Studies have demonstrated the role of neutrophil extracellular traps (NETs) in the process of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the underlying mechanism remains unclear. In this study, the regulation of Nrf2 in the fo...

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Main Authors: Junying Lu, Guilan Xiong, Hongxiang Li, Dong Zhang, Xiaohao Zhang
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2024/8847492
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author Junying Lu
Guilan Xiong
Hongxiang Li
Dong Zhang
Xiaohao Zhang
author_facet Junying Lu
Guilan Xiong
Hongxiang Li
Dong Zhang
Xiaohao Zhang
author_sort Junying Lu
collection DOAJ
description The pathogenesis of acute lung injury is complex. Studies have demonstrated the role of neutrophil extracellular traps (NETs) in the process of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the underlying mechanism remains unclear. In this study, the regulation of Nrf2 in the formation of NETs, which was pathogenic in LPS-induced ALI, was identified by analyzing the levels of Cit-H3, lung function, lung tissue pathology, lung wet/dry ratio, the inflammatory cells, cytokines and proteins in the bronchoalveolar lavage fluid (BALF) and in addition, the activity of lung myeloperoxidase (MPO) was also measured. Results showed that the levels of Cit-H3 measured by western blot in Nrf2-knockout (KO) mice were higher compared with the WT mice after LPS stimulation. To further investigate the NETs formation was pathogenic during LPS-induced ALI, the Nrf2-KO mice were treated with DNase I. Results showed that DNase I improved lung function and lung tissue pathology and significantly reduced lung wet/dry ratio and proteins in the BALF. Besides, DNase I also attenuated the infiltration of inflammatory cells and the cytokines (TNF-α, IL-1β) production in the BALF and the activity of lung MPO. Therefore, these results together indicate that Nrf2 may intervene in the release of NETs during LPS-induced ALI in mice.
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spelling doaj-art-5de4f364c82346aba61b88a16fb757a82025-02-02T22:57:35ZengWileyMediators of Inflammation1466-18612024-01-01202410.1155/2024/8847492Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in MiceJunying Lu0Guilan Xiong1Hongxiang Li2Dong Zhang3Xiaohao Zhang4Department of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineDepartment of Critical Care MedicineDepartment of CardiologyThe pathogenesis of acute lung injury is complex. Studies have demonstrated the role of neutrophil extracellular traps (NETs) in the process of lipopolysaccharide (LPS)-induced acute lung injury (ALI). However, the underlying mechanism remains unclear. In this study, the regulation of Nrf2 in the formation of NETs, which was pathogenic in LPS-induced ALI, was identified by analyzing the levels of Cit-H3, lung function, lung tissue pathology, lung wet/dry ratio, the inflammatory cells, cytokines and proteins in the bronchoalveolar lavage fluid (BALF) and in addition, the activity of lung myeloperoxidase (MPO) was also measured. Results showed that the levels of Cit-H3 measured by western blot in Nrf2-knockout (KO) mice were higher compared with the WT mice after LPS stimulation. To further investigate the NETs formation was pathogenic during LPS-induced ALI, the Nrf2-KO mice were treated with DNase I. Results showed that DNase I improved lung function and lung tissue pathology and significantly reduced lung wet/dry ratio and proteins in the BALF. Besides, DNase I also attenuated the infiltration of inflammatory cells and the cytokines (TNF-α, IL-1β) production in the BALF and the activity of lung MPO. Therefore, these results together indicate that Nrf2 may intervene in the release of NETs during LPS-induced ALI in mice.http://dx.doi.org/10.1155/2024/8847492
spellingShingle Junying Lu
Guilan Xiong
Hongxiang Li
Dong Zhang
Xiaohao Zhang
Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
Mediators of Inflammation
title Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_full Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_fullStr Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_full_unstemmed Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_short Nuclear Factor Erythroid 2-Related Factor 2 Intervenes the Release of Neutrophil Extracellular Traps during Lipopolysaccharide-Induced Acute Lung Injury in Mice
title_sort nuclear factor erythroid 2 related factor 2 intervenes the release of neutrophil extracellular traps during lipopolysaccharide induced acute lung injury in mice
url http://dx.doi.org/10.1155/2024/8847492
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