NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis

Zhao-ming Chen; Jia-hui He; Rui-di Tang; Jun-qing Yue; Xiao-xian Zhang; Zhen-feng He; Shao-Qiang Li; Hui-Min Li; Xiao-fen Zhang; Lai-jian Cen; Cui-xia Pan; Ming-xin Shi; Sheng-zhu Lin; Shu-Jun Guo; Wei-jie Guan

doi:10.34133/research.0958

journal article Jan 01, 2025

NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis

Zhao-ming Chen Jia-hui He Rui-di Tang Jun-qing Yue Xiao-xian Zhang Zhen-feng He Shao-Qiang Li Hui-Min Li Xiao-fen Zhang Lai-jian Cen Cui-xia Pan Ming-xin Shi Sheng-zhu Lin Shu-Jun Guo

Wei-jie Guan

Research Vol. 8 · American Association for the Advancement of Science (AAAS)

View at Publisher Save 10.34133/research.0958

Abstract

Neutrophilic inflammation and
Pseudomonas aeruginosa
infection have been implicated in the pathogenesis and progression of bronchiectasis. However, the mechanisms underlying the inflammasome activation and neutrophil extracellular traps (NETs) formation, which are triggered by lipopolysaccharide (LPS), thereby fostering relentless neutrophilic inflammation and airway destruction, remain poorly understood. Here, we investigated how nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation modulates NET formation, epithelial inflammation, and injury in bronchiectasis. Compared with those in the stable state, interleukin-1β levels in the exacerbation state were greater and were correlated with blood neutrophil counts. LPS triggered neutrophil NLRP3 inflammasome activation and induced NET formation. At exacerbation, caspase-1 p20, DNA-myeloperoxidase, and DNA-neutrophil elastase expression levels were increased compared with those in the stable state. LPS triggered the first signal, nuclear factor-κB, for NLRP3 inflammasome activation within the airway epithelium, leading to neutrophil chemotactic factor release. NETs served as the secondary signal for thorough NLRP3 inflammasome activation. Acting synergistically with LPS, NETs amplified epithelial inflammation, up-regulating mucin 5AC expression while suppressing zona occludens-1 and α-tubulin expression. Both MCC950 and Z-VAD-FMK inhibited NLRP3 inflammasome activation, whereas GSK484 and LDC7559 suppressed NET formation. Collectively, NLRP3 inflammasome activation facilitates NET formation in bronchiectasis, aggravating inflammation and eliciting injury to epithelial cells.

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Details

Published: Jan 01, 2025
Vol/Issue: 8

Authors

Z

Zhao-ming Chen

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

J

Jia-hui He

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.; Division of Respiratory Medicine and Gastroenterology, University of Dundee, Ninewells Hospital and Medical School

R

Rui-di Tang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.; Guangzhou National Laboratory

J

Jun-qing Yue

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.; Guangzhou National Laboratory

X

Xiao-xian Zhang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

Z

Zhen-feng He

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

S

Shao-Qiang Li

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

H

Hui-Min Li

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

X

Xiao-fen Zhang

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

L

Lai-jian Cen

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

C

Cui-xia Pan

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

M

Ming-xin Shi

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

S

Sheng-zhu Lin

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

S

Shu-Jun Guo

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.

W

Wei-jie Guan

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, National Center for Respiratory Medicine, Joint International Research Laboratory of Respiratory Health, Guangdong Basic Research Center of Excellence for Respiratory Medicine, Department of Allergy and Clinical Immunology, Department of Respiratory and Critical Care Medicine, Guangzhou Institute of Respiratory Health, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510163, P. R. China.; Guangzhou National Laboratory; China-Portugal Artificial Intelligence and Public Health Technologies Joint Laboratory, Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Diseases, Guangdong Provincial Key Laboratory of Respiratory Disease Research, Guangzhou Medical University; Shanxi Bethune Hospital

Funding

National Natural Science Foundation Award: No. 82470040

Noncommunicable Chronic Diseases-National Science and Technology Major Project Award: No. 2024ZD0529600, No. 2024ZD0529601

Major Project of Guangzhou National Laboratory Award: GZNL2024A02003

National Natural Science Foundation - Outstanding Youth Fund Award: No. 82222001

Guangzhou Science and Technology Plans Award: No. 2024A04J6495, 2024A03J1206, 2023B03J0407

Plan on Enhancing Scientific Research in Guangzhou Medical University Award: grant number not applicable

Cite This Article

Zhao-ming Chen, Jia-hui He, Rui-di Tang, et al. (2025). NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis. Research, 8. https://doi.org/10.34133/research.0958

NLRP3 Inflammasome Activation Modulates Neutrophil Extracellular Trap Formation and Aggravates Airway Inflammation in Bronchiectasis

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