中性粒细胞胞外陷阱
自噬
丁酸钠
PI3K/AKT/mTOR通路
化学
激酶
蛋白激酶B
蛋白激酶A
细胞外
安普克
丁酸盐
髓过氧化物酶
丁酸
细胞生物学
生物
生物化学
信号转导
细胞凋亡
炎症
免疫学
基因
发酵
作者
Yuhang Li,Juxiong Liu,Yueyao Cui,Yu Cao,Ping Xu,Xingchi Kan,Wenjin Guo,Shoupeng Fu
标识
DOI:10.1016/j.intimp.2022.109009
摘要
Neutrophil extracellular traps (NETs) are an important means by which the body fights against exogenous bacteria. However, studies have shown that excessive NETs release can damage other cells. Accumulating evidence has shown that butyric acid can alleviate the inflammatory response of cells. However, the effect of butyric acid on Staphylococcus aureus-induced NETs formation and its underlying mechanism are still unclear. In this study, western blotting, immunofluorescence and CCK-8 assays were used to examine the effect of NETs formation by sodium butyrate (NaB). The results showed that NaB suppressed the release of S. aureus-induced NETs formation, as indicated by decreases in the levels of DNA, histones, myeloperoxidase, and neutrophil elastase. S. aureus can induce autophagy, and autophagy plays a key role in the formation of NETs. Our data showed that NaB activated mammalian target of rapamycin (mTOR) and the kinases protein kinase B (AKT) and unc-51 like kinase 1 (ULK1) at Ser757 and inhibited AMP-activated protein kinase (AMPK). To explore whether NaB inhibited the formation of NETs by inhibiting autophagy, we added 3-methyladenine (autophagy inhibitor) (3-MA, 5 mM) to bovine neutrophils, and the results showed that 3-MA significantly inhibited NETs release. Furthermore, we found that NETs and their component histones exhibited significantly increased the cytotoxic effects on bovine mammary epithelial cells (BMECs), indicating that NETs and their component histones play a key role in BMEC damage. In conclusion, NaB can reduce the excessive formation of NETs by inhibiting autophagy, thus reducing the damaging effect of NETs on BMECs.
科研通智能强力驱动
Strongly Powered by AbleSci AI