Cigarette smoke extract modulates Pseudomonas aeruginosa bacterial load via USP25/HDAC11 axis in lung epithelial cells.

Abstract

Cigarette smoking increases susceptibility for microbial infection in respiratory system. However, the underlying molecular mechanism(s) is not fully elucidated. Here we report that cigarette smoking extract (CSE) increases bacterial load in lung epithelial cells via downregulation of USP25/HDAC11 axis. CSE treatment decreases HDAC11 at protein level in lung epithelial cells without significant changes of its transcription. Concomitantly, CSE treatment accelerates a ubiquitin specific protease USP25 ubiquitination and degradation. Co-immunoprecipitation studies showed that USP25 associated with HDAC11. USP25 catalyzes de-ubiquitination of HDAC11, which regulates HDAC11 protein stability. CSE-mediated degradation of USP25 thereafter reduces HDAC11 at protein level. Interestingly, CSE-downregulated USP25/HDAC11 axis increases the bacterial load of Pseudomonas aeruginosa in lung epithelial cells. These findings suggest that CSE-downregulated USP25 and HDAC11 may contribute to high susceptibility of bacterial infection in the cigarette smoking population.