Acrolein induced both pulmonary inflammation and the death of lung epithelial cells

• Published in: Toxicology letters Vol. 229; no. 2; pp. 384 - 392
• Main Authors: Sun, Yang, Ito, Sachiko, Nishio, Naomi, Tanaka, Yuriko, Chen, Nana, Isobe, Ken-ichi
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ireland Ltd 02.09.2014
• Subjects: Acrolein - toxicity; Acroleins; Activated; Animals; Apoptosis - drug effects; Blotting, Western; Cigarettes; Cytokines; Cytokines - analysis; Cytokines - biosynthesis; Female; Flow Cytometry; Inhibitors; Lung - chemistry; Lung - cytology; Lung - drug effects; Lungs; Macrophage Activation - drug effects; Macrophages; Mice; Mice, Inbred C57BL; NF-kappa B - drug effects; Pneumonia - chemically induced; Reactive Oxygen Species - analysis; Real-Time Polymerase Chain Reaction; Respiratory Mucosa - drug effects; Signal Transduction - drug effects; Smoke; Transcription Factor RelA - drug effects
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2014.06.021

•Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases.•Acrolein increased CD11c+F4/80high macrophages in the lungs.•Acrolein increased ROS formation via induction of NF-κB signaling.•Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Acrolein, a compound found in cigarette smoke, is a major risk factor for respiratory diseases. Previous research determined that both acrolein and cigarette smoke produced reactive oxygen species (ROS). As many types of pulmonary injuries are associated with inflammation, this study sought to ascertain the extent to which exposure to acrolein advanced inflammatory state in the lungs. Our results showed that intranasal exposure of mice to acrolein increased CD11c+F4/80high macrophages in the lungs and increased ROS formation via induction of NF-κB signaling. Treatment with acrolein activated macrophages and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. In in vitro studies, acrolein treatment of bone marrow-derived GM-CSF-dependent immature macrophages (GM-IMs), activated the cells and led to their increased production of ROS and expression of several key pro-inflammatory cytokines. Acrolein treatment of macrophages induced apoptosis of lung epithelial cells. Inclusion of an inhibitor of ROS formation markedly decreased acrolein-mediated macrophage activation and reduced the extent of epithelial cell death. These results indicate that acrolein can cause lung damage, in great part by mediating the increased release of pro-inflammatory cytokines/factors by macrophages.