SIRT1 protects against urban particulate matter-induced airway inflammation

Abstract

Tianwen Lai,* Xiaoxia Wen,* Dong Wu,* Guomei Su, Yun Gao, Cuifen Chen, Weiquan Wu, Yingying Lv, Zhanghui Chen, Quanchao Lv, Wen Li, Dongming Li, Min Chen, Bin WuDepartment of Respiratory and Critical Care Medicine, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, People’s Republic of China*These authors contributed equally to this workPurpose: Particulate matter (PM) has been implicated as a risk factor for airway injury. However, the molecular mechanisms remain largely unclear. The goal of this study was to determine whether sirtuin1 (SIRT1), an anti-inflammatory and antiaging protein, protects against PM-induced airway inflammation.Methods: The effect of SIRT1 on PM-induced airway inflammation was assessed by using in vivo models of airway inflammation induced by PM and in vitro culture of human bronchial epithelial (HBE) cells exposed to PM, resveratrol (SIRT1 activator), or both.Results: PM-stimulated HBE cells showed a significant decrease in SIRT1 but a notable increase in inflammatory cytokines. SIRT1 gene silencing further enhanced PM-induced expression of inflammatory cytokines. In contrast, resveratrol, a SIRT1 activator, reduced the expression of these cytokines compared with the control cells. In vivo, SIRT1 expression was significantly decreased in lung tissues of PM-exposed mice. Interestingly, resveratrol treatment reversed the enhanced total cells, neutrophils and inflammatory cytokines in PM-induced mice. Moreover, SIRT1 mediated PM-induced inflammatory cytokines expression at least partly through MAPK pathways.Conclusion: These findings suggest that SIRT1 is involved in the pathogenesis of PM-induced airway inflammation and activation of SIRT1 could prevent airway disorders or disease exacerbations induced by airborne particulate pollution.Keywords: particulate matter, SIRT1, resveratrol, airway inflammation

Keywords

• Particulate matter
• SIRT1
• Resveratrol
• Airway inflammation