Bronchial epithelial pyroptosis promotes airway inflammation in a murine model of toluene diisocyanate-induced asthma. 2020

Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
Department of Rheumatology and Immunology, The Third Affiliated Hospital, Southern Medical University, Institute of Clinical Immunology, Academy of Orthopedics of Guangdong Province, Guangdong Provincial Key Laboratory of Bone and Joint Degenerative Diseases, Guangzhou, Guangdong, China.

Airway epithelial injury in response to allergens such as toluene diisocyanate (TDI) leads to persistent airway inflammation. Pyroptosis is recognized as a strong proinflammatory cell death process. However, the role of pyroptosis in bronchial epithelial injury and airway inflammation in TDI-induced asthma remains unknown. In this study, cytotoxic effect of TDI on 16HBE cells (a human bronchial epithelial cell line) was detected. Then a TDI-induced experimental asthma mouse model was established for in vivo study. Here we found that TDI induced pyroptosis in 16HBE cells, as evidenced by enhanced expressions of caspase-1 and elevated levels of LDH, IL-1β and HMGB1. As expected, TDI-induced inflammatory cell death was significantly blocked by a specific NLRP3 inflammasome inhibitor. Intriguingly, in asthmatic mice, the increased cleavages of caspase-1 and pyroptotic executioner gasdermin D (GSDMD) in bronchial epithelial cells were decreased by NLRP3 inflammasome inhibitor. Furthermore, inhibition of NLRP3 inflammasome attenuated airway hyper-responsiveness and airway inflammation, accompanied by lower levels of IL-1β, IgE and Th2-related cytokines. Our data suggest that bronchial epithelial pyroptosis exacerbates airway inflammation and hyper-responsiveness in TDI-induced asthma via NLRP3 inflammasome activation and GSDND cleavage. Therefore, NLRP3 inflammasome-mediated pyroptosis may be a potential treatment target for TDI-induced asthma.

UI MeSH Term Description Entries
D007249 Inflammation A pathological process characterized by injury or destruction of tissues caused by a variety of cytologic and chemical reactions. It is usually manifested by typical signs of pain, heat, redness, swelling, and loss of function. Innate Inflammatory Response,Inflammations,Inflammatory Response, Innate,Innate Inflammatory Responses
D008297 Male Males
D008807 Mice, Inbred BALB C An inbred strain of mouse that is widely used in IMMUNOLOGY studies and cancer research. BALB C Mice, Inbred,BALB C Mouse, Inbred,Inbred BALB C Mice,Inbred BALB C Mouse,Mice, BALB C,Mouse, BALB C,Mouse, Inbred BALB C,BALB C Mice,BALB C Mouse
D012130 Respiratory Hypersensitivity A form of hypersensitivity affecting the respiratory tract. It includes ASTHMA and RHINITIS, ALLERGIC, SEASONAL. Airway Hyperresponsiveness,Hypersensitivity, Respiratory,Airway Hyper-Responsiveness,Airway Hyper Responsiveness,Airway Hyperresponsivenesses,Hyper-Responsiveness, Airway,Hyperresponsiveness, Airway,Respiratory Hypersensitivities
D001980 Bronchi The larger air passages of the lungs arising from the terminal bifurcation of the TRACHEA. They include the largest two primary bronchi which branch out into secondary bronchi, and tertiary bronchi which extend into BRONCHIOLES and PULMONARY ALVEOLI. Primary Bronchi,Primary Bronchus,Secondary Bronchi,Secondary Bronchus,Tertiary Bronchi,Tertiary Bronchus,Bronchi, Primary,Bronchi, Secondary,Bronchi, Tertiary,Bronchus,Bronchus, Primary,Bronchus, Secondary,Bronchus, Tertiary
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004847 Epithelial Cells Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells. Adenomatous Epithelial Cells,Columnar Glandular Epithelial Cells,Cuboidal Glandular Epithelial Cells,Glandular Epithelial Cells,Squamous Cells,Squamous Epithelial Cells,Transitional Epithelial Cells,Adenomatous Epithelial Cell,Cell, Adenomatous Epithelial,Cell, Epithelial,Cell, Glandular Epithelial,Cell, Squamous,Cell, Squamous Epithelial,Cell, Transitional Epithelial,Cells, Adenomatous Epithelial,Cells, Epithelial,Cells, Glandular Epithelial,Cells, Squamous,Cells, Squamous Epithelial,Cells, Transitional Epithelial,Epithelial Cell,Epithelial Cell, Adenomatous,Epithelial Cell, Glandular,Epithelial Cell, Squamous,Epithelial Cell, Transitional,Epithelial Cells, Adenomatous,Epithelial Cells, Glandular,Epithelial Cells, Squamous,Epithelial Cells, Transitional,Glandular Epithelial Cell,Squamous Cell,Squamous Epithelial Cell,Transitional Epithelial Cell
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000069292 Pyroptosis Type of programmed cell death associated with infection by intracellular pathogens. It is characterized by INFLAMMASOME formation; activation of CASPASE 1; and CYTOKINES mediated inflammation. Caspase-1 Dependent Cell Death,Inflammatory Apoptosis,Pyroptotic Cell Death,Apoptoses, Inflammatory,Apoptosis, Inflammatory,Caspase 1 Dependent Cell Death,Cell Death, Pyroptotic,Cell Deaths, Pyroptotic,Death, Pyroptotic Cell,Deaths, Pyroptotic Cell,Inflammatory Apoptoses,Pyroptoses,Pyroptotic Cell Deaths

Related Publications

Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
January 1991, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
May 2004, The Journal of allergy and clinical immunology,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
March 2006, FEBS letters,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
February 2022, BMC pulmonary medicine,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
February 2021, Toxicology in vitro : an international journal published in association with BIBRA,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
January 1992, The American review of respiratory disease,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
October 2005, The Journal of allergy and clinical immunology,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
August 2019, Toxicological sciences : an official journal of the Society of Toxicology,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
July 2011, Allergy, asthma & immunology research,
Jian Zhuang, and Haiyan Cui, and Lili Zhuang, and Zeqing Zhai, and Fangyuan Yang, and Guihu Luo, and Juan He, and Haijin Zhao, and Wenqu Zhao, and Yi He, and Erwei Sun
September 2012, International journal of occupational medicine and environmental health,
Copied contents to your clipboard!