Research Paper Volume 10, Issue 6 pp 1415—1423
Induction of neutrophil apoptosis by a Bcl-2 inhibitor reduces particulate matter-induced lung inflammation
- 1 Department of Pharmacology and Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China
- 2 Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital, Institute of Respiratory Diseases, Zhejiang University School of Medicine, Hangzhou 310009, China
- 3 State Key Laboratory of Respiratory Diseases, Guangzhou, Guangdong 510120, China
received: March 16, 2018 ; accepted: June 10, 2018 ; published: June 26, 2018 ;https://doi.org/10.18632/aging.101477
How to Cite
Copyright: Geng et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Environmental particulate matter exposure can cause various respiratory problems including aggravated asthma, decreased lung function and increased respiratory symptoms. However, the molecular mechanisms underlying PM-induced lung inflammation are incompletely understood. Effective therapeutic strategies are required.
A mouse model of particulate matter-induced lung inflammation was used to identify the pathology and the molecular mechanisms for particulate matter-induced lung inflammation. The mouse model revealed that particulate matter induced neutrophil-dominated lung inflammation. Neutrophils derived from particulate matter-instilled mice showed decreased apoptosis and elevated Bcl-2 expression. Further studies in vav-Bcl-2 transgenic mice made it clear that Bcl-2 overexpression caused a marked increase in neutrophils in bronchoalveolar lavage fluid. Furthermore, we found that the Bcl-2 inhibitor ABT-199 reduced particulate matter-induced lung inflammation, and induced apoptosis of neutrophils in particulate matter-induced lung inflammation mice model.
Particulate matter-induced lung inflammation is mediated in part by inhibition of apoptosis of inflammatory cells. Bcl-2 is responsible for the reduced apoptosis of inflammatory cells in particulate matter-induced lung inflammation. The Bcl-2 selective inhibitor ABT-199 reduces particulate matter-induced lung inflammation by inducing the apoptosis of neutrophils and might be a promising drug for the treatment of particulate matter-induced lung inflammation.