Involvement of reactive oxygen species in the metabolic pathways triggered by diesel exhaust particles in human airway epithelial cells

Abstract

Diesel exhaust particles (DEP) induce a proinflammatory response in human bronchial epithelial cells (16HBE) characterized by the release of proinflammatory cytokines after activation of transduction pathways involving MAPK and the transcription factor NF-kappaB. Because cellular effects induced by DEP are prevented by antioxidants, they could be mediated by reactive oxygen species (ROS). Using fluorescent probes, we detected ROS production in bronchial and nasal epithelial cells exposed to native DEP, organic extracts of DEP (OE-DEP), or several polyaromatic hydrocarbons. Carbon black particles mimicking the inorganic part of DEP did not increase ROS production. DEP and OE-DEP also induced the expression of genes for phase I [cytochrome P-450 1A1 (CYP1A1)] and phase II [NADPH quinone oxidoreductase-1 (NQO-1)] xenobiotic metabolization enzymes, suggesting that DEP-adsorbed organic compounds become bioavailable, activate transcription, and are metabolized since the CYP1A1 enzymatic activity is increased. Because NQO-1 gene induction is reduced by antioxidants, it could be related to the ROS generated by DEP, most likely through the activation of the stress-sensitive Nrf2 transcription factor. Indeed, DEP induced the translocation of Nrf2 to the nucleus and increased protein nuclear binding to the antioxidant responsive element. In conclusion, we show that DEP-organic compounds generate an oxidative stress, activate the Nrf2 transcription factor, and increase the expression of genes for phase I and II metabolization enzymes.

Proteomics-based safety evaluation of multi-walled carbon nanotubes

“…Iron and PAHs have been reported to contribute to the oxidation reaction (Baulig et al, 2003;Kagan et al, 2006;Guo et al, 2007;Byrne and Baugh, 2008;Liu et al, 2008). Thus, we thought that the impurities (iron and PAHs) in MWCNTs cause the inhibition of cell proliferation.…”

Activation of Pulmonary Dendritic Cells and Th2-Type Inflammatory Responses on Instillation of Engineered, Environmental Diesel Emission Source or Ambient Air Pollutant Particles in vivo

“…It has been shown that ambient PM also induces epithelial cells to produce amphiregulin, granulocyte-macrophage colony-stimulating factor and MIP-3 ␣ [53][54][55][56] , that are known to induce recruitment and survival of DC. It seems likely therefore that DC will be among the first cells to sense and respond to inhaled PM, although the importance of bronchial/pulmonary epithelial cells cannot be overlooked.…”

Pollution atmosphérique et maladies respiratoires

“…Les métaux de transition, fer, cuivre et vanadium, subissent des cycles d'oxydoréduction au cours desquels ils produisent le radical hydroxyl, très réactif. Les composés organiques induisent une production d'ERO spécifiquement dans des macrophages [8] et dans des cellules épi-théliales bronchiques humaines [9] par l'intermédiaire des quinones, capables de générer des radicaux libres au cours de cycles rédox [10], et des hydrocarbures aromatiques polycycliques (HAP) dont la méta-bolisation conduit également à la formation d'ERO.…”

“…Ils induisent l'expression et l'activité du cytochrome P450 1A1 (CYP 1A1), enzyme de métabolisation de phase I [15]. Les ERO produites par l'activité propre de l'enzyme, ainsi que par les métabolites, contribuent à l'activation de facteurs de transcription sensibles au stress oxydant dont NF-κB mais aussi Nrf2 [9], qui participe à l'activation de l'élément de réponse aux anti-oxydants (ARE). Celui-ci contrôle les gènes de métabolisation d'enzymes de phase II et d'enzymes à activité anti-oxydante telles que l'hème oxygénase.…”