S1P/HDAC1 Signaling Regulates Macrophage Polarization in Patients with Chronic Obstructive Pulmonary Disease

Throughout the world, chronic obstructive pulmonary disease (COPD) is the cause of substantial morbidity and mortality and represents a large public health burden. Previous studies reported that inflammation is intimately involved in COPD, but the underlying mechanism remains unclear. As macrophage polarization was demonstrated to regulate inflammation, we hypothesized that COPD alters macrophage polarization. To test this, we investigated in individuals with COPD the relationship between S1PR1 and HADC1 expression and macrophage inflammation via flow cytometry, qRT-PCR, gene knockdown/overexpression, and western blot analysis. We found that macrophages from COPD subjects were polarized towards an M1 phenotype with increased S1PR1 and decreased HADC1experssion. S1PR1 also inhibited HADC1 expression. Thus, S1PR1/HDAC1 signaling regulates macrophage polarization. The results from this study provide insights into the pathogenesis of COPD and suggest possible therapeutic opportunities.