title: NLRP3 inflammasome activation by mitochondrial ROS in bronchial epithelial cells is required for allergic inflammation.
abstract: Abnormality in mitochondria has been suggested to be associated with development of allergic airway disorders. In this study, to evaluate the relationship between mitochondrial reactive oxygen species (ROS) and NLRP3 inflammasome activation in allergic asthma, we used a newly developed mitochondrial ROS inhibitor, NecroX-5. NecroX-5 reduced the increase of mitochondrial ROS generation in airway inflammatory cells, as well as bronchial epithelial cells, NLRP3 inflammasome activation, the nuclear translocation of nuclear factor-κB, increased expression of various inflammatory mediators and pathophysiological features of allergic asthma in mice. Finally, blockade of IL-1β substantially reduced airway inflammation and hyperresponsiveness in the asthmatic mice. These findings suggest that mitochondrial ROS have a critical role in the pathogenesis of allergic airway inflammation through the modulation of NLRP3 inflammasome activation, providing a novel role of airway epithelial cells expressing NLRP3 inflammasome as an immune responder.
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University - Biomedical Research Institute of Chonbuk National University Hospital, Deokjin-gu, Jeonju, South Korea.
authors.forename: S R
authors.initials: SR
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University - Biomedical Research Institute of Chonbuk National University Hospital, Deokjin-gu, Jeonju, South Korea.
authors.forename: D I
authors.initials: DI
authors.lastname: Kim
authors.affiliation: Department of Product Strategy and Development, LG Life Sciences Ltd, Seoul, Korea.
authors.forename: S H
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University - Biomedical Research Institute of Chonbuk National University Hospital, Deokjin-gu, Jeonju, South Korea.
authors.forename: H
authors.initials: H
authors.lastname: Lee
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University - Biomedical Research Institute of Chonbuk National University Hospital, Deokjin-gu, Jeonju, South Korea.
authors.forename: K S
authors.initials: KS
authors.lastname: Lee
authors.affiliation: Division of Allergy-Immunology, Department of Medicine, Northwestern University, Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Cho
authors.affiliation: Department of Internal Medicine, Research Center for Pulmonary Disorders, Chonbuk National University Medical School, Research Institute of Clinical Medicine of Chonbuk National University - Biomedical Research Institute of Chonbuk National University Hospital, Deokjin-gu, Jeonju, South Korea.
authors.forename: Y C
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000818:Animals; D001249:Asthma / Q000097:blood / Q000473:pathology; D001980:Bronchi / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002352:Carrier Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D004272:DNA, Mitochondrial / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D006576:Heterocyclic Compounds, 4 or More Rings / Q000494:pharmacology; D006801:Humans; D006967:Hypersensitivity / Q000378:metabolism / Q000473:pathology*; D058847:Inflammasomes / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000378:metabolism; D042541:Intracellular Space / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008297:Male; D051379:Mice; D008875:Middle Aged; D008928:Mitochondria / Q000378:metabolism*; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D010047:Ovalbumin; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013450:Sulfones / Q000494:pharmacology; D014132:Trachea / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D004272:DNA, Mitochondrial; D006576:Heterocyclic Compounds, 4 or More Rings; D058847:Inflammasomes; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; C574766:NecroX-5; C492716:Nlrp3 protein, mouse; D017382:Reactive Oxygen Species; D013450:Sulfones; D010047:Ovalbumin; D009195:Peroxidase; D020170:Caspase 1