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Regulatory effect of NLRP3 on airway inflammatory response and pyroptosis in mice with asthma.

OBJECTIVES
To study the regulatory effect of the NOD-like receptor, pyrin domain-containing 3 (NLRP3) on airway inflammatory response and pyroptosis in mice with asthma.


METHODS
The NLRP3 wild-type (WT) C57BL/6J mice were divided into two groups: NLRP3-WT control and NLRP3-WT asthma. The mice with NLRP3 knockout (KO) were divided into two groups: NLRP3-KO control and NLRP3-KO asthma (n=10 each). A model of asthma was prepared by intraperitoneal injection of ovalbumin + aluminium hydroxide for sensitization and ovalbumin inhalation for challenge. Enhanced pause, an index for airway responsiveness, was measured for each group. Hematoxylin and eosin staining was used to observe the histomorphological changes of lungs and determine the inflammation score for each group. Bronchoalveolar lavage fluid was collected from each group to determine the numbers of neutrophils, eosinophils, and lymphocytes and measure the content of interleukin-1β (IL-1β) and interleukin-18 (IL-18). Western blot was used to measure the expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue of each group.


RESULTS
Compared with the NLRP3-WT control group, the NLRP3-WT asthma group showed morphological changes including airway smooth muscle thickening and inflammatory cell infiltration. Compared with the NLRP3-WT asthma group, the NLRP3-KO asthma group had significant improvements in the above morphological manifestations. Compared with the NLRP3-WT control group, the NLRP3-WT asthma group had significant increases in the enhanced pause, the inflammation score of lung tissue, the numbers of neutrophils, eosinophils and lymphocytes in bronchoalveolar lavage fluid, and the levels of IL-1β and IL-18 in bronchoalveolar lavage fluid (P<0.05). The expression of NLRP3, cleaved caspase-1, and Gasdermin D-N in lung tissue also significantly increased in the NLRP3-WT asthma group (P<0.05). The above indices in the NLRP3-KO asthma group were significantly lower than those in the NLRP3-WT asthma group (P<0.05).


CONCLUSIONS
The overexpression of NLRP3 is associated with the pathogenesis of asthma, which may be related to the molecular mechanisms of the activation of airway inflammatory response and pyroptosis. Citation.