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

Chen Long; Yandong Lai; Tiao Li; Toru Nyunoya; Chunbin Zou

doi:10.1152/ajplung.00142.2019

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

Journal article

Open access

Peer reviewed

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

Chen Long, Yandong Lai, Tiao Li, Toru Nyunoya and Chunbin Zou

American journal of physiology. Lung cellular and molecular physiology, Vol.318(2), pp.L252-L263

02/01/2020

DOI: 10.1152/ajplung.00142.2019

PMCID: PMC7034647

PMID: 31746627

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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 the ubiquitin-specific protease 25 (USP25)/histone deacetylase 11 (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. Coimmunoprecipitation studies showed that USP25 associated with HDAC11. USP25 catalyzes deubiquitination of HDAC11, which regulates HDAC11 protein stability. CSE-mediated degradation of USP25 thereafter reduces HDAC11 at the protein level. Interestingly, CSE-downregulated USP25/HDAC11 axis increases the bacterial load of 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.

Signal Transduction

Animals

Bacterial Load - physiology

Cell Line

Cigarette Smoking - adverse effects

Enzyme Stability

Female

Histone Deacetylases - metabolism

Humans

Lung - metabolism

Lung - microbiology

Lysine - metabolism

Male

Mice, Inbred C57BL

Models, Biological

Polyubiquitin - metabolism

Proteasome Endopeptidase Complex - metabolism

Proteolysis

Pseudomonas aeruginosa - physiology

Ubiquitin Thiolesterase - metabolism

Ubiquitination

Details

Title: Subtitle: Cigarette smoke extract modulates Pseudomonas aeruginosa bacterial load via USP25/HDAC11 axis in lung epithelial cells
Creators: Chen Long - University of Pittsburgh School of Medicine
Yandong Lai - University of Pittsburgh
Tiao Li - University of Pittsburgh
Toru Nyunoya - University of Pittsburgh
Chunbin Zou - University of Pittsburgh
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.318(2), pp.L252-L263
DOI: 10.1152/ajplung.00142.2019
PMID: 31746627
PMCID: PMC7034647
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: American Physiological Society
Grant note: R01 HL125435 / NHLBI NIH HHS R01 HL149719 / NHLBI NIH HHS I01 CX000105 / CSRD VA R01 HL142997 / NHLBI NIH HHS I01 CX001048 / CSRD VA
Language: English
Date published: 02/01/2020
Academic Unit: Internal Medicine
Record Identifier: 9985217143802771

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