title: Activation of Transcription Factors by Diesel Exhaust Particles in Human Bronchial Epithelial Cells in Vitro.
abstract: Diesel exhaust particles (DEP) are suspected to be involved in the aggravation of inflammatory respiratory diseases. We have shown previously, in human bronchial epithelial cell line 16HBE 14o-, that DEP induced the release of the proinflammatory cytokines granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-8 (IL-8) after 24 h of exposure. Gene expression of these cytokines is regulated by transcription factors including NF-κB and AP-1, which are known to be sensitive to oxidative stress. Their activation by DEP was investigated in comparison with a pure oxidant, H2O2 A 4-h exposure to DEP (10 μg/cm(2)) or to H2O2 (100 µM) increased NF-κB DNA binding in 16HBE cells as assessed by electrophoretic mobility shift assay. AP-1 was only activated by H202 in the same conditions. Organic extracts of DEP increased NF-κB DNA binding as did native DEP, suggesting the role of the polycyclic aromatic hydrocarbons (PAH) in this NF-κB increased DNA binding. Dimethylthiourea (DMTU), an antioxidant, inhibited the NF-κB DNA binding induced by DEP, suggesting an involvement of reactive oxygen species (ROS) in the transduction pathways leading to NF-κB activation. Moreover, the MEK pathway inhibitor PD98059 inhibited DEP-induced NF-κB DNA binding. The role of Erk 1/2 was likely implicated, since DEP induced an increase of Erk phosphorylation.
authors.affiliation: a Laboratoire de Cytophysiologie et Toxicologie Cellulaire , Université Paris , Paris , France.
authors.forename: V
authors.initials: V
authors.lastname: Bonvallot
authors.affiliation: a Laboratoire de Cytophysiologie et Toxicologie Cellulaire , Université Paris , Paris , France.
authors.forename: A
authors.initials: A
authors.lastname: Baeza-Squiban
authors.affiliation: a Laboratoire de Cytophysiologie et Toxicologie Cellulaire , Université Paris , Paris , France.
authors.forename: S
authors.initials: S
authors.lastname: Boland
authors.affiliation: a Laboratoire de Cytophysiologie et Toxicologie Cellulaire , Université Paris , Paris , France.
authors.forename: F
authors.initials: F
authors.lastname: Marano