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NLRP3 inflammasome-related pyroptosis aggravates the airway inflammation in toluene diisocyanate-induced asthmatic mice

NLRP3 inflammasome-related pyroptosis aggravates the airway ...

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第十三届全国免疫学学术大会

作者： Jian Zhuang Yi He Haiyan Cui Guihu Luo Fangyuan Yang Zeqing Zhai Yanan Zhang Erwei Sun The Third Affiliated Hospital of Southern Medical University

Background: toluene diisocyanate(TDI), the most common inhalation of occupational asthma, is proven to drive bronchial epithelium damage and IL-1β production in patients with TDI-induced asthma and asthmatic *** a kind of proinflammatory cell death, NLRP3 inflammasome-related pyroptosis is characterized by cell injury and IL-1β *** this study, we investigated whether NLRP3 inflammasome-related pyroptosis was implicated in the development of bronchial epithelial cell injury and airway inflammation in TDI-induced ***: 16 HBE cells(a human bronchial epithelial cell line) were stimulated with TDI-HSA conjugates in *** cell viability, and the concentrations of LDH, IL-1β and IL-18 in the supernatant were *** vivo, male BALF/c mice were sensitized and challenged with TDI to establish asthma ***950, the specific inhibitor of NLRP3 inflammasome, was administered by intraperitoneal *** the airway hyperresponsiveness(AHR) and airway inflammation in TDI-induced asthmatic mice were ***: TDI-HSA conjugates reduced the bronchial epithelial cell viability in a time and dose-dependent ***, TDI-HSA increased the ratio of caspase-1PI cells, as well as the levels of LDH, IL-1β and ***, MCC950 significantly blocked TDI-HSA-induced bronchial epithelial *** TDI-induced asthmatic mice, administration with MCC950 attenuated AHR and airway inflammatory cell infiltration by inhibiting the activation of caspase-1 and pyroptotic executioner GSDMD in the ***, NLRP3 inflammasome inhibitor could decrease the levels of IL-1β in the plasma and BALF, accompanied by lower concentrations of IgE in the plasma and Th2-related cytokines in the ***: These data suggested that bronchial epithelial pyroptosis played a critical role in the pathogenesis of TDI-induced asthma via activation of NLRP3 inflammasome, and cleavage of caspase-1 and ***, inhibition of NLRP3 inflammas

关键词： toluene diisocyanate-induced asthma NLRP3 inflammasome Bronchial epithelial pyroptosis

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