PM2.5 augments cigarette smoke-induced lung inflammation in mice by driving a stronger immune response: Potential beneficial effects of oleanolic acid.

Though cigarette smoke (CS) is primary risk factor for Chronic obstructive pulmonary disease (COPD), rising air pollution and higher concentrations of particulate matter (PM2.5) in ambient air contribute substantially to COPD cases, particularly in smokers. However, the pathogenesis of COPD upon dual exposure to CS and PM2.5 is not entirely known. Therefore, the impact of combined exposure to CS (9 cigarettes/day for 4 days) and PM2.5 (single dose of 50 μg) on COPD pathogenesis was examined using mouse model in order to understand the key players behind the process. The data suggest that single exposure to PM2.5 in CS pre-exposed mice triggered a strong inflammatory response, marked by switch from macrophage to neutrophilic inflammation, leading to severe deterioration in lung function compared to single hits. Furthermore, combined exposure led to robust increase in the levels of pro-inflammatory cytokines (G-CSF/KC/MCP-1/TNF-α/IL-1β/IL-6) in BALF as compared to the respective individual exposure. Interestingly, Oleanolic acid (OA) treatment protects against CS + PM2.5-induced COPD-like pulmonary inflammation potentially by exerting antioxidant properties as reflected by data on BALF inflammatory cells, particularly neutrophils and various oxidative stress markers such as ROS/LPO/GSH/SOD/Catalase in lung tissue. Suppressed inflammation was associated with downregulation of gene expression of pro-inflammatory factors namely IL-1β, TNF-α, MIP-2 and normalization of proteinase-antiproteinase balance by downregulating gene expression of MMP-9 with simultaneous upregulation of its inhibitor TIMP-1. Reduced inflammatory response upon OA treatment correlates well with improved lung function. Overall, PM2.5 exposure flares up the CS-induced lung inflammation linked to COPD, which is effectively ameliorated by OA.