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

Abstract

Purpose: Particulate matter (PM_2.5) 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 PM_2.5-induced airway inflammation in macrophages.

Methods: The effect of SIRT6 on PM_2.5-induced airway inflammation was assessed by using THP1 cells or bone marrow-derived macrophages (BMDMs) exposed to PM_2.5 in vitro and myeloid cell-specific SIRT6 conditional knockout mice (Sirt6^fl/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 PM_2.5. In vivo, Sirt6^fl/fl-LysMCre mice substantially decreased airway inflammation in response to PM_2.5 exposure.

Conclusion: Our results revealed that SIRT6 promotes the PM_2.5-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: SIRT6; lung inflammation; macrophage; particulate matter.