Myeloid-Specific SIRT6 Deletion Protects Against Particulate Matter (PM2.5)-Induced Airway Inflammation

Shaopeng Chen,1,2,* Mindan Wu,3,* Zhilin Xiong,1,* Jiewen Huang,1 Yingying Lv,1 Yuyan Li,4 Minjuan Zeng,5 Tianwen Lai1 1Institute of Respiratory Diseases, The First Dongguan Affiliated Hospital of Guangdong Medical University, Dongguan, People’s Republic of China; 2Blood Donation Service Department, Zhanjiang Blood Center, Zhanjiang, People’s Republic of China; 3Department of Pulmonary and Critical Care Medicine, Shantou Central Hospital, Shantou, People’s Republic of China; 4Department of Pulmonary and Critical Care Medicine, Dongguan Hospital of Southern Medical University, Dongguan, People’s Republic of China; 5Laboratory Animal Center, Guangdong Medical University, Zhanjiang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Tianwen Lai; Minjuan Zeng, Email laitianwen2011@163.com; mjzeng@gdmu.edu.cnPurpose: Particulate matter (PM2.5) is a common risk factor for airway inflammation. Alveolar macrophages play a critical role in airway inflammation. Sirtuin 6 (SIRT6) is a class Ill histone deacetylase that exerts an anti-inflammatory effect in airway diseases. However, the role of SIRT6 on PM2.5-induced airway inflammation in macrophages remains unclear. We aimed to determine whether SIRT6 protects against PM2.5-induced airway inflammation in macrophages.Methods: The effect of SIRT6 on PM2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6fl/fl-LysMCre) in vivo.Results: PM2.5 increased SIRT6 expression in THP1 cells, but SIRT6 gene silencing decreased PM2.5 induced inflammatory cytokines in THP1 cells. Moreover, the expression of SIRT6 and inflammatory cytokines was also decreased in BMDMs with myeloid-specific deletion of SIRT6 after stimulation of PM2.5. In vivo, Sirt6fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM2.5 exposure.Conclusion: Our results revealed that SIRT6 promotes the PM2.5-induced airway inflammation in macrophages and indicated that inhibition of SIRT6 in macrophages may represent therapeutic strategy for airway disorders induced by airborne particulate pollution.Keywords: particulate matter, SIRT6, macrophage, lung inflammation