Isoquercitrin inhibits Streptococcus pneumoniae-induced pyroptosis of BEAS-2B cells by SIRT1-mediated acetylation
Abstract
Pyroptosis, a pro-inflammatory form of cell death, critically contributes to the pathogenesis of pneumonia. Isoquercitrin (IQC), a flavonoid with established anti-inflammatory properties, was investigated for its potential to mitigate pyroptosis in bronchial epithelial cells and its underlying mechanism. BEAS-2B cells were injured by Streptococcus pneumoniae (SP) infection and subsequently treated with IQC. Pyroptosis was assessed using flow cytometry, enzyme-linked immunosorbent assay, and western blotting. The interaction between IQC and SIRT1 was examined by molecular docking and surface plasmon resonance. The acetylation of NLRP3 regulated by SIRT1 was evaluated through immunoprecipitation (IP)/co-IP, cycloheximide chase assay, and western blotting. Results indicated that IQC enhanced cell viability and suppressed SP-induced pyroptosis. IQC was found to bind directly to SIRT1 and upregulate its protein expression. Furthermore, SIRT1 knockdown promoted NLRP3 acetylation and increased its protein stability. The anti-pyroptotic effect of IQC was abolished by SIRT1 silencing, and NLRP3 overexpression reversed the pyroptosis suppression resulting from SIRT1 overexpression. In conclusion, IQC attenuates SP-induced pyroptosis by enhancing SIRT1 expression, which facilitates the deacetylation of NLRP3. These findings identify IQC as a promising therapeutic candidate for pneumonia.
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