title: The Nucleotide-Binding Oligomerization Domain-Like Receptor Family Pyrin Domain-Containing 3 Inflammasome Regulates Bronchial Epithelial Cell Injury and Proapoptosis after Exposure to Biomass Fuel Smoke.
abstract: The number of individuals in the population exposed to biomass fuel smoke (BS) is far greater than the number of cigarette smokers. About 20% of cigarette smokers develop chronic obstructive pulmonary disease (COPD) due to smoke-induced irreversible damage and sustained inflammation of the airway epithelium. However, the role of BS in COPD pathogenesis remains to be elucidated. In this study, we investigated the expression of nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 and caspase-1 in the bronchial epithelium from patients with COPD, and further determined the specific role of the NLRP3 inflammasome in bronchial epithelium injury using two in vitro models (BS and cigarette smoke [CS]) in the human bronchial epithelial (HBE) cell line (16HBE). After exposure to BS and CS, the release of damage-associated molecular patterns, the transcriptional and translational up-regulation of NLRP3, and the activation of caspase-1 were observed in cells at different time points. Because IL-1β secretion was dependent on the NLRP3 inflammasome, we assessed CXCL-8 production in response to smoke. Using a transwell migration assay in which 16HBE cells and human alveolar macrophages were cocultured, we showed that smoke-induced NLRP3 activation in 16HBE cells increased the migration of human alveolar macrophages. When the NLRP3 expression was silenced, the average migration distance of 16HBE was increased in scratch assay, because the activation of NLRP3 induced apoptosis by the p53-Bax mitochondrial pathway in the smoke-induced response. These results demonstrate the importance of the NLRP3 inflammasome in mediating BS- and CS-induced HBE cell damage and proapoptosis.
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Li
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Huang
authors.initials: H
authors.lastname: Zhihong
authors.affiliation: 2 Department of Pathology, Sun Yat-Sen University Cancer Center; State Key Laboratory of Oncology in South China, Guangzhou, Guangdong, China; and.
authors.forename: Li
authors.initials: L
authors.lastname: Wenlong
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Xiaoyan
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Qing
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Luo
authors.initials: L
authors.lastname: Wenzhi
authors.affiliation: 3 Medical College, Jinan University, Guangzhou, Guangdong, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Siming
authors.affiliation: 1 Department of Respiratory Medicine, First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Shengming
mesh_terms: D000368:Aged; D017209:Apoptosis; D018533:Biomass; D001980:Bronchi / Q000473:pathology*; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D016207:Cytokines / Q000378:metabolism; D003710:Demography; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D018384:Oxidative Stress; D029424:Pulmonary Disease, Chronic Obstructive / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D058847:Inflammasomes; D018836:Inflammation Mediators; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D012906:Smoke
keywords: alveolar macrophages; biomass fuel smoke; bronchial epithelial cells; nucleotide-binding oligomerization domain–like receptor family pyrin domain-containing 3