Induction of neutrophil apoptosis by a Bcl-2 inhibitor reduces particulate matter-induced lung inflammation

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  • 作者:Xinwei Geng, Xiaohui Wang, Man Luo, Meichun Xing, Yinfang Wu, Wen Li, Zhihua Chen, Huahao Shen, Songmin Ying
  • 期刊:Aging-US
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BackgroundEnvironmental 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.ResultsA 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.ConclusionsParticulate 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.

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