title: Enriched inorganic compounds in diesel exhaust particles induce mitogen-activated protein kinase activation, cytoskeleton instability, and cytotoxicity in human bronchial epithelial cells.
abstract: This study assessed the effects of the diesel exhaust particles on ERK and JNK MAPKs activation, cell rheology (viscoelasticity), and cytotoxicity in bronchial epithelial airway cells (BEAS-2B). Crude DEP and DEP after extraction with hexane (DEP/HEX) were utilized. The partial reduction of some DEP/HEX organics increased the biodisponibility of many metallic elements. JNK and ERK were activated simultaneously by crude DEP with no alterations in viscoelasticity of the cells. Mitochondrial activity, however, revealed a decrease through the MTT assay. DEP/HEX treatment increased viscoelasticity and cytotoxicity (membrane damage), and also activated JNK. Our data suggest that the greater bioavailability of metals could be involved in JNK activation and, consequently, in the reduction of fiber coherence and increase in the viscoelasticity and cytotoxicity of BEAS cells. The adverse findings detected after exposure to crude DEP and to DEP/HEX reflect the toxic potential of diesel compounds. Considering the fact that the cells of the respiratory epithelium are the first line of defense between the body and the environment, our data contribute to a better understanding of the pathways leading to respiratory cell injury and provide evidence for the onset of or worsening of respiratory diseases caused by inorganic compounds present in DEP.
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Robson
authors.initials: R
authors.lastname: Seriani
authors.affiliation: Central Biotery Laboratory, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Mara S
authors.initials: MS
authors.lastname: Junqueira
authors.affiliation: Laboratory of Chronopharmacology, Department of Physiology, Institute of Bioscience, University of São Paulo, São Paulo, São Paulo, Brazil.
authors.forename: Claudia E
authors.initials: CE
authors.lastname: Carvalho-Sousa
authors.affiliation: Experimental Therapeutics Laboratory, Department of Medicine, School of Medicine, University of São Paulo, Brazil.
authors.forename: Alessandra C T
authors.initials: AC
authors.lastname: Arruda
authors.affiliation: Laboratory of Microrheology and Molecular Physiology, Institute of Physics, University of São Paulo, São Paulo, Brazil.
authors.forename: Diana
authors.initials: D
authors.lastname: Martinez
authors.affiliation: Laboratory of Microrheology and Molecular Physiology, Institute of Physics, University of São Paulo, São Paulo, Brazil.
authors.forename: Adriano M
authors.initials: AM
authors.lastname: Alencar
authors.affiliation: PREMIUM Confocal Microscopy Core Facility, University of São Paulo, Brazil.
authors.forename: Ana L
authors.initials: AL
authors.lastname: Garippo
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Jôse Mara
authors.initials: JM
authors.lastname: Brito
authors.affiliation: Experimental Therapeutics Laboratory, Department of Medicine, School of Medicine, University of São Paulo, Brazil.
authors.forename: Milton A
authors.initials: MA
authors.lastname: Martins
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Paulo H N
authors.initials: PH
authors.lastname: Saldiva
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Elnara M
authors.initials: EM
authors.lastname: Negri
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.
authors.forename: Thais
authors.initials: T
authors.lastname: Mauad
authors.affiliation: Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil. Electronic address: mmacchione@lim05.fm.usp.br.
authors.forename: Mariangela
authors.initials: M
authors.lastname: Macchione
mesh_terms: D001980:Bronchi / Q000187:drug effects; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000187:drug effects*; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects*; D006801:Humans; D007287:Inorganic Chemicals / Q000633:toxicity; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D052638:Particulate Matter / Q000633:toxicity*; D020545:Respiratory Mucosa / Q000187:drug effects*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D007287:Inorganic Chemicals; D052638:Particulate Matter; D001335:Vehicle Emissions; D020928:Mitogen-Activated Protein Kinases
keywords: Cell viscoelasticity; Cytotoxicity; Diesel exhaust particles; MAPKs; Metals