Fine particulate matter exposure promotes M2 macrophage polarization through inhibiting histone deacetylase 2 in the pathogenesis of chronic obstructive pulmonary disease.

Abstract

BackgroundChronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality globally. Fine particulate matter (PM2.5) has been indicated to be a major detrimental risk factor for COPD by numerous epidemiological studies. Histone deacetylase 2 (HDAC2), a critical regulator of chromatin remodeling, plays a pivotal role in the development of COPD. However, the underlying mechanisms regarding the relationship between PM2.5 and HDAC2 in the pathogenesis of COPD have yet to be elucidated. In the present study, we aim to investigate the role and the underlying mechanism of HDAC2 in the development of PM2.5-induced COPD.MethodsThe effects of PM2.5 exposure on M2 macrophage polarization and the expression levels of HDAC2 were examined in vitro. The influence of HDAC2 deficiency on M2 macrophage polarization and the pathogenesis of COPD was investigated in a PM2.5-induced mouse model.ResultsPM2.5 exposure down-regulated the protein level of HDAC2 and enhanced M2 macrophage polarization in vitro. In the COPD murine model, myeloid-specific deficiency of HDAC2 augmented PM2.5-induced M2 polarization of alveolar macrophages (AMs) and up-regulation of tumor necrosis factor (TGF)-β, matrix metallopeptidase (MMP)-9, and MMP-12 in lung tissue, which resulted in more prominent lung function deterioration, airspace enlargement, alveolar wall destruction, and airway remodeling, indicating a key role of HDAC2 in the pathogenesis of PM2.5-induced COPD.ConclusionsPM2.5 facilitated M2 polarization by inhibiting HDAC2, leading to the development of COPD. Targeting of HDAC2 would provide a novel approach to prevent the development of PM2.5 exposure-induced COPD.