Diesel exhaust particles induce an inflammatory response in airway epithelial cells: Involvement of reactive oxygen species

Epidemiological studies have shown that high particulate air pollution is associated with an increase in hospital admissions for respiratory diseases and with an exacerbation of asthma symptoms [8]. In urban areas, traffic appears to be the main source of particulate airborne pollutants. Diesel engine powered cars, which produce the most abundant components of PM2.5 (Particulate Matter 2.5 µm), are suspected to be responsible for this exacerbation of respiratory diseases but their real impact on health has not been fully elucidated. Recent experimental studies have emphasized the role of diesel exhaust particles (DEP) in the development of an inflammatory response. Nasal challenges of humans with DEP result in the local increase in IgE and cytokine production [7]. In vitro studies have shown that airway epithelial cells, one of the main cellular targets of DEP, directly participate in this inflammatory response [2]. Indeed, cultured human nasal and bronchial epithelial cells exposed to DEP released in a time and dose dependent process, proinflammatory cytokines such as GM-CSF and IL-8 known to be involved in allergic diseases [3]. This increased release of GM-CSF has been shown to be subsequent to transcription [4]. Since airway epithelial cells can be effectors of the inflammatory response, it is necessary to investigate the cellular and molecular mechanisms leading to this response and to determine the respective role of DEP components in these mechanisms. DEP are composed of a carbonaceous core with adsorbed organic compounds (polyaromatic hydrocarbons (PAH), nitroaromatic hydrocarbons, quinones, aldehydes and aliphatic hydrocarbons) which could represent up to 60% of the mass of the particle depending on the vehicle and the fuel composition. The cellular and molecular events induced by DEP were investigated using a model of bronchial epithelial cells, the human bronchial epithelial cell line (16HBE 14 o-) and standard reference DEP (SRM 1650). The effects of native DEP were compared to those induced by the organic extracts of DEP (OE-DEP) obtained by extraction of DEP with dichloromethan and by the carbonaceous core represented either by carbon black particles or stripped DEP (sDEP) recovered after extraction. DEP trigger MAPK Erk 1/2 signalling pathways as a specific inhibitor of this pathway (PD 98059) clearly reduced the DEP-induced GM-CSF release. Moreover the phosphorylated form of Erk 1/2