Fine Particulate Matter and Sulfur Dioxide Coexposures Induce Rat Lung Pathological Injury and Inflammatory Responses Via TLR4/p38/NF-κB Pathway

Abstract

Fine particulate matter (PM2.5) and sulfur dioxide (SO2) are 2 common air pollutants, but their toxicological effects of coexposure are still not fully clear. In this study, SO2 exposure (5.6 mg/m3) couldn’t cause obvious inflammatory responses in rat lungs. The PM2.5 exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO2 and PM2.5 (1.5, 6.0, and 24.0 mg/kg) coexposure induced pathological and ultrastructural damage and raised inflammatory cells in BALF compared with the control. Also, they significantly elevated the levels of pro-inflammatory cytokines, adhesion molecule, and nitric oxide (NO) and promoted the gene expression of nuclear factor kappa B (NF-κB), phosphorylated p38 (p-p38), and Toll-like receptor 4 (TLR4) in rat lungs treated with higher dose of PM2.5 (6.0 and 24.0 mg/kg) plus SO2 relative to the control or SO2 group, along with the decreased inhibitor of NF-κBα and increased inhibitor of NF-κB kinase β expressions. The changes in the inflammatory markers in the presence of PM2.5 plus SO2 were not significant compared with the PM2.5 group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM2.5 plus SO2 were involved in TLR4/p38/NF-κB pathway activation accompanied by oversecretion of pro-inflammatory cytokine, adhesion molecule, and NO. It provides more useful evidence to understand the possible toxicological mechanism that PM2.5 and SO2 copollution exacerbate lung disease.