Brd4 inhibition ameliorates Pyocyanin-mediated macrophage dysfunction via transcriptional repression of reactive oxygen and nitrogen free radical pathways.

ABSTRACT: Macrophages play critical roles in the first-line immune defense against airway infections caused by Pseudomonas aeruginosa (PA). The redox-active phenazine-pyocyanin (PCN), as one of the most essential virulence factors, facilities PA-related infection via a wide spectrum of cellular oxidative damages. However, little is known for PCN cytotoxicity in macrophages. In this study, besides showing PCN-mediated reactive oxygen species (ROS) indeed involved in macrophage viability and function impairment, we at the first time demonstrated a novel role of reactive nitrogen species (RNS) pathway causing cellular damage in PCN-challenged macrophages. Using small molecule inhibitor JQ1 targeting Bromodomain and extra-terminal family proteins, we showed restrained iNOS-dependent nitric oxide (NO) pr

SUBMITTER: Zhu F 

PROVIDER: S-EPMC7295752 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature