Tobramycin-induced secretion of P. aeruginosa 5′ tRNA-fMet halves suppresses lung inflammation via AGO2 gene silencing
biorxiv(2021)
摘要
Although inhaled tobramycin increases lung function in people with cystic fibrosis (pwCF), the density of P. aeruginosa in the lungs is only modestly reduced by tobramycin; hence, the mechanism whereby tobramycin improves lung function is unclear. Here, we demonstrate that tobramycin increases the abundance of two 5′ tRNA-fMet halves in outer membrane vesicles (OMVs) secreted by P. aeruginosa and that the 5′ tRNA-fMet halves reduce IL-8 secretion by CF bronchial epithelial cells (CF-HBECs). In mouse lung, the 5′ tRNA-fMet halves attenuate KC secretion and neutrophil recruitment. We also report that the 5′ tRNA-fMet halves suppress pro-inflammatory network gene expression by an Argonaut 2 (AGO2)-mediated gene silencing mechanism, thereby reducing IL-8 secretion in CF-HBECs. Moreover, tobramycin reduces the IL-8 concentration and neutrophil content in bronchoalveolar lavage fluid of pwCF. Thus, we conclude that tobramycin improves lung function in part by reducing chronic inflammation and neutrophil-mediated lung damage in pwCF.
### Competing Interest Statement
The authors have declared no competing interest.
更多查看译文
AI 理解论文
溯源树
样例
生成溯源树,研究论文发展脉络
Chat Paper
正在生成论文摘要