title: 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, SO2exposure (5.6 mg/m3) couldn't cause obvious inflammatory responses in rat lungs. The PM2.5exposure (1.5 mg/kg body weight) increased inflammatory cell counts in bronchoalveolar lavage fluid (BALF) and some inflammation damage. Importantly, SO2and 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 SO2relative to the control or SO2group, 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 PM2.5plus SO2were not significant compared with the PM2.5group. The results indicated that inflammatory injury and pathological and ultrastructural damage in rat lungs exposed to PM2.5plus SO2were 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 PM2.5and SO2copollution exacerbate lung disease.
authors.affiliation: 1 Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Ruijin
authors.initials: R
authors.lastname: Li
authors.affiliation: 1 Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Lifang
authors.initials: L
authors.lastname: Zhao
authors.affiliation: 1 Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Tong
authors.affiliation: 1 Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Yuchao
authors.initials: Y
authors.lastname: Yan
authors.affiliation: 1 Institute of Environmental Science, Shanxi University, Taiyuan, People's Republic of China.
authors.forename: Chong
authors.initials: C
authors.lastname: Xu
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004347:Drug Interactions; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D016328:NF-kappa B / Q000276:immunology; D009569:Nitric Oxide / Q000276:immunology; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D052638:Particulate Matter / Q000633:toxicity*; D012333:RNA, Messenger / Q000378:metabolism; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013458:Sulfur Dioxide / Q000633:toxicity*; D051197:Toll-Like Receptor 4 / Q000276:immunology; D048051:p38 Mitogen-Activated Protein Kinases / Q000276:immunology
chemical_list: D000393:Air Pollutants; D016207:Cytokines; D016328:NF-kappa B; D052638:Particulate Matter; D012333:RNA, Messenger; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D013458:Sulfur Dioxide; D018799:Intercellular Adhesion Molecule-1; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D048051:p38 Mitogen-Activated Protein Kinases
keywords: coexposure; fine particulate matter; inflammation; pathology; rat lung; sulfur dioxide