title: Differential proinflammatory responses induced by diesel exhaust particles with contrasting PAH and metal content.
abstract: Exposure to diesel engine exhaust particles (DEPs), representing a complex and variable mixture of components, has been linked with cellular production and release of several types of mediators related to pulmonary inflammation. A key challenge is to identify the specific components, which may be responsible for these effects. The aim of this study was to compare the proinflammatory potential of two DEP-samples with contrasting contents of polycyclic aromatic hydrocarbons (PAHs) and metals. The DEP-samples were compared with respect to their ability to induce cytotoxicity, expression and release of proinflammatory mediators (IL-6, IL-8), activation of mitogen-activated protein kinases (MAPKs) and expression of CYP1A1 and heme oxygenase-1 (HO-1) in human bronchial epithelial (BEAS-2B) cells. In addition, dithiothreitol and ascorbic acid assays were performed in order to examine the oxidative potential of the PM samples. The DEP-sample with the highest PAH and lowest metal content was more potent with respect to cytotoxicity and expression and release of proinflammatory mediators, CYP1A1 and HO-1 expression and MAPK activation, than the DEP-sample with lower PAH and higher metal content. The DEP-sample with the highest PAH and lowest metal content also possessed a greater oxidative potential. The present results indicate that the content of organic components may be determinant for the proinflammatory effects of DEP. The findings underscore the importance of considering the chemical composition of particulate matter-emissions, when evaluating the potential health impact and implementation of air pollution regulations.
authors.affiliation: Division of Environmental Medicine, Department of Air Pollution and Noise, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Annike I
authors.initials: AI
authors.lastname: Totlandsdal
authors.forename: Marit
authors.initials: M
authors.lastname: Låg
authors.forename: Edel
authors.initials: E
authors.lastname: Lilleaas
authors.forename: Flemming
authors.initials: F
authors.lastname: Cassee
authors.forename: Per
authors.initials: P
authors.lastname: Schwarze
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D008670:Metals / Q000032:analysis / Q000633:toxicity*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D052638:Particulate Matter / Q000633:toxicity*; D011084:Polycyclic Aromatic Hydrocarbons / Q000032:analysis / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D001335:Vehicle Emissions / Q000032:analysis / Q000633:toxicity*
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D018836:Inflammation Mediators; D008670:Metals; D052638:Particulate Matter; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; D001335:Vehicle Emissions; D019363:Cytochrome P-450 CYP1A1; D051547:Heme Oxygenase-1; D020928:Mitogen-Activated Protein Kinases
keywords: PAH; diesel engine exhaust particles; epithelial lung cells; inflammation; metals