Identifying the key chemical compounds and source contributions in ambient particles associated with the burden of cardiopulmonary disease is important to develop cost-effective air pollution mitigating strategies that maximize the protection of public health. To help address this need, we examined 109 daily ambient fine particulate matter samples (PM2.5) that were collected in Beijing in one year. The samples were analyzed for chemical composition including organic and elemental carbons, metals, ions, as well as organic molecular markers. In addition, the secretion of pro-inflammatory cytokines, tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were measured by exposing lung epithelial cells (A549) to water extracts of PM2.5 samples. Single pollutant and constituent-PM2.5 joint linear models were used to estimate the associations. Higher PM2.5 mass and measured chemical components were found in cold seasons than in warm seasons due to the greater contributions of secondary inorganic sources, biomass burning, and coal combustion. Water-soluble organic nitrogen (WSON) had the strongest associations with levels of pro-inflammatory cytokines compared to PM2.5 mass and other chemical species in both the one and constituent-PM2.5 joint linear models. Our study is the first to highlight that ambient WSON from diverse sources dominates the inflammatory potential of lung epithelial cells.