The Effect of Myricetin on Streptococcus Pneumoniae-Induced Pyroptosis of Alveolar Epithelial Cells by Modulating NLRP3/Caspase-1/IL-1β Signaling Pathway
Objective To investigate the effect of myricetin(MYR)on alveolar epithelial cell pyroptosis induced by Streptococcus pneumoniae through modulating NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteine protease-1(Caspase-1)/interleukin-1β(IL-1β)signaling pathway.Methods Human type Ⅱ alveolar epithelial cells(AT Ⅱ.)were randomly separated into five groups:control group,model group,L-MYR group(20μg/mL),M-MYR group(40μg/mL),H-MYR group(80μg/mL),and ATP group(80μg/mL MYR+2 mmol/L NLRP3/Caspase-1/IL-1β signaling pathway activator ATP).Except for applying the normal culture condition in the control group,the damage model was established with Streptococcus pneumoniae infection in all the other groups.MTT and plate cloning method were used to detect the proliferation of cells.TUNEL was used to detect pyroptosis of cells.ELISA was applied to detect the levels of interleukin-1β(IL-1β),interleukin-18(IL-18),and lactate dehydrogenase(LDH).Western blot was used to detect the protein expressions of NLRP3,cleaved caspase-1,pyocorin D(GSDMD)and IL-1β.Results Compared with the control group,A490 and the number of clones in the model group decreased,while the cell pyroptosis rate,and the expressions of IL-1β,IL-18,LDH,NLRP3,cleaved caspase-1,GSDMD and IL-1βincreased(P＜0.05).Compared with the model group,A490 and the number of clones in the L-MYR group,M-MYR group and H-MYR group increased,while the cell pyroptosis rate,and the expressions of IL-1β,IL-18,LDH,NLRP3,cleaved caspase-1,GSDMD and IL-1β decreased(P＜0.05).Compared with the H-MYR group,A490 and the number of clones in the ATP group decreased,while the cell pyroptosis rate,and the expressions of IL-1β,IL-18,LDH,NLRP3,cleaved caspase-1,GSDMD and IL-1β increased(P＜0.05).Conclusion MYR could alleviate the inflammatory response of alveolar epithelial cells induced by Streptococcus pneumoniae through inhibiting the NLRP3/Caspase-1/IL-1β signaling pathway,thereby inhibiting cell pyroptosis.
MyricetinNOD-like receptor thermal protein domain associated protein 3/cysteine protease-1/interleukin-1β signaling pathwayStreptococcus pneumoniae infectionPyroptosis
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