Effect of Regulating the NLRP3/Caspase-1/IL-1β Signaling Pathway on Streptococcus pneumoniae-Induced Pyroptosis in Alveolar Epithelial Cells
TAN Huafa
ZHANG Yiwei
Abstract：Objective To investigate the effect of regulating the nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)/caspase-1/interleukin-1β(IL-1β)signaling pathway on Streptococcus pneumoniae-induced pyroptosis in alveolar epithelial cells.Methods Sixty SPF-grade healthy adult SD rats were randomly divided into four groups according to a random number table:control group,model group,inhibition group,and activation group,with 15 rats in each group.The control group received 0.1 mL of 0.9%sodium chloride solution via tracheal injection,while the model,inhibition,and activation groups received 0.1 mL of Streptococcus pneumoniae solution via tracheal injection.After successful modeling,the inhibition group received an intraperitoneal injection of MCC950 at 60 mg/kg,and the activation group received an intraperitoneal injection of 1 mg/mL BMS-986299 prepared in sterilized Milli-Q water at 10 mg/kg.The control and model groups received an equal volume of 0.9%sodium chloride solution via intraperitoneal injection.Serum levels of NLRP3,caspase-1,and IL-1β were observed and compared among the four groups before injection and at 1,3,12,and 24 hours after injection.Alveolar pathology and alveolar epithelial cell pyroptosis were also examined 24 hours after injection.Results Compared with the control group,the model,inhibition,and activation groups all showed significantly elevated serum levels of NLRP3,Caspase-1,and IL-1β both before and after injection(P<0.05).At 3,12,and 24 hours after injection,all measured indices in the inhibition group were significantly lower than those in the model group(P<0.05),while the activation group showed significantly higher NLRP3 and Caspase-1 levels at these same time points,along with significantly higher IL-1β levels at 24 hours compared to the model group(P<0.05).Furthermore,the activation group demonstrated significantly higher NLRP3 and Caspase-1 levels at 3,12,and 24 hours after injection,as well as higher IL-1β levels at 1,3,12,24 hour,compared to the inhibition group(P<0.05).At 24 hours post-injection,all three intervention groups exhibited more severe acute lung injury and pyroptosis compared to the control group.Relative to the model group,the inhibition group showed significant alleviation of both lung injury and pyroptosis,whereas the activation group demonstrated marked exacerbation.Acute lung injury score analysis revealed that the model,inhibition,and activation groups all had significantly higher scores than the control group(P<0.05).The inhibition group score was significantly lower than that of the model group,while the activation group score was significantly higher than both the model and inhibition groups(P<0.05).Conclusion Regulating the expression levels of proteins in the NLRP3/caspase-1/IL-1β signaling pathway can alleviate or promote Streptococcus pneumoniae-induced pyroptosis in alveolar epithelial cells.The NLRP3/caspase-1/IL-1β signaling pathway may serve as a therapeutic target for pulmonary diseases caused by Streptococcus pneumoniae infection.
Keywords：alveolar epithelial cellsstreptococcus pneumoniaepyroptosisratsnucleotide-binding oligomerization domain-like receptor protein 3Caspase-1interleukin-1β
Publication Date：2025-12-20
Online Publishing Date：2025-12-25(First online date of this platform, not the publication date of the document)
Pages：7( 129-135 )