Stilbenoid gaylussacin modulates particulate matter-induced chromatin remodeling in macrophages to suppress chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD), a leading cause of mortality worldwide, is characterized by chronic bronchitis and emphysema. 1 Current treatment offers symptomatic relief but minimally affect disease progression. 2 Cigarette smoke (CS) is the primary risk factor; but airborne particulate matter (PM) also contributes and synergizes with CS to accelerate disease progression. Dysregulated macrophages drive COPD pathogenesis by inducing inflammation and tissue destruction through excessive secretion of cytokines, reactive oxygen and nitrogen species (ROS/RNS), and proteases. 1 We previously showed that PM exposure induces macrophage infiltration in the lungs of mice, wherein enhanced CCCTC-binding factor (CTCF) binding to the promoters of kynurenine pathway (KP) enzyme genes ( Kmo , Kynu , Haao , and Qprt ) reduces NAD + synthesis, inactivates SIRT1, increases histone acetylation, and induces proinflammatory gene expression during COPD development. 3 These effects were reversed by resveratrol, a stilbenoid SIRT1 activator. 3