Indirect effect of PM1 on endothelial cells via inducing the release of respiratory inflammatory cytokines

Abstract A large number of epidemiological studies have shown that increased cardiovascular morbidity and mortality are associated with exposure to high concentrations of PM 2.5 . One of the ways that PM 2.5 affects the cardiovascular system is through systemic inflammation. Inflammatory cytokines such as TNF-α, IL-1β, IL-6, and IL-8 stimulate endothelial cells, which leads to endothelial dysfunction. Compared with PM 2.5 , PM 1 is smaller in size, has a larger surface area and absorbs more toxic substances such as heavy metals, organic compounds, and black carbon. However, the effect of PM 1 on human health is less studied. Here, we used BEAS-2B cells and differentiated THP-1 cells to simulate epithelial cells and macrophages in the lung, respectively. The indirect effect of PM 1 on endothelial cells was studied with a coculture model consisting of two cell lines (BEAS-2B cells and macrophages) in the top compartment and one cell line, human umbilical vein endothelial cells (EA.hy926), in the bottom compartment of a transwell plate. The results showed that PM 1 could promote the release of inflammatory cytokines, including TNF-α and IL-6, from BEAS-2B cells and macrophages. In addition, PM 1 upregulated ICAM-1 expression in EA.hy926 cells through TNF-α/NF-κB signaling pathways, promoting the adhesion of endothelial cells and monocytes, a key event in the initiation of atherosclerosis.