title: NLRP3 inflammasome is essential for the development of chronic obstructive pulmonary disease.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is now recognized as an inflammatory disease and the nucleotide-binding oligomerization domain-like receptor 3 (NLRP3) inflammasome was speculated to participate into its pathophysiological process, however, a direct role of NLRP3 has yet to be clearly shown.
  
  
  METHODS
  COPD model was established by tobacco inhalation, COPD modeling and NLRP3 knockout mice were treated with similar dose and duration of tobacco inhalation for 12 months, the lung function, lung damage and immune responses were evaluated between control, wild type COPD and NLRP3 knock out C57B1/6 mice.
  
  
  RESULTS
  10 months after tobacco inhalation, the respiratory system resistance indexes of COPD mice was significantly higher than that of control and NLRP3 knockout mice (2.8 ± 0.5 vs. 1.2 ± 0.3 and 1.3 ± 0.1 cm H2O ml(-1) s(-1), P < 0.05); the respiratory system compliance indexes of COPD was significantly lower than that of control and NLRP3 knockout mice (0.31 ± 0.02 vs. 0.43 ± 0.04, and 0.39 ± 0.01 ml/cm H2O); the NLRP3 knockout mice displayed no distinguishable pathological damage in the lung. Of the broncho-alveolar lavage fluid (BALF), the concentration of IL-1 and IL-18 of the COPD were significantly higher than that of control and NLRP3 knockout mice (IL-1: 286.8 ± 1.7 vs. 23.8 ± 2.1 and 24.2 ± 1.3 pg/mL, P < 0.05; IL-18: 104.5 ± 4.2 vs. 12.6 ± 2.1 and 15.7 ± 2.8 pg/mL, P < 0.05); the total numbers of macrophages, eosinophils, lymphocyte and neutrophil of control, COPD and NLRP3 knockout mice were 2.3 ± 0.4, 0.5 ± 0.2, 10.3 ± 3.4 and 2.8 ± 2.7; 8.7 ± 1.1, 12.5 ± 1.1, 45.3 ± 3.3 and 29.2 ± 4.2; and 3.2 ± 0.7, 1.8 ± 0.4, 18.1 ± 1.1 and 12.8 ± 3.4 × 10(4) mL, respectively; the rates of NLRP3 positive macrophages in the BALF of control, COPD and NLRP3 knockout mice were 5.0 ± 1.0%, 78.1 ± 9.2% and 2.0 ± 0.9%, respectively.
  
  
  CONCLUSIONS
  NLRP3 inflammasome is essential for the development of COPD and blockade of NLRP3 might be a possible therapeutic strategy for COPD.
authors.affiliation: Department of Respiration, The Shanghai First People's Hospital of Baoshan Branch 101 North Tongtai Road, Shanghai 200940, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Respiration, The Shanghai First People's Hospital of Baoshan Branch 101 North Tongtai Road, Shanghai 200940, China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ni
authors.affiliation: Department of Respiration, The Shanghai First People's Hospital of Baoshan Branch 101 North Tongtai Road, Shanghai 200940, China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Respiration, The Shanghai First People's Hospital of Baoshan Branch 101 North Tongtai Road, Shanghai 200940, China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Gu
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000473:pathology*
chemical_list: D002352:Carrier Proteins; D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse
keywords: Chronic obstructive pulmonary disease; inflammasome; nucleotide-binding oligomerization domain-like receptor 3