Diesel exhaust particles induce CYP1A1 and pro-inflammatory responses via differential pathways in human bronchial epithelial cells

<p>Abstract</p> <p>Background</p> <p>Exposure to diesel engine exhaust particles (DEPs) has been associated with several adverse health outcomes in which inflammation seems to play a key role. DEPs contain a range of different inorganic and organic compounds, including polycyclic aromatic hydrocarbons (PAHs). During the metabolic activation of PAHs, CYP1A1 enzymes are known to play a critical role. In the present study we investigated the potential of a characterised sample of DEPs to induce cytotoxicity, to influence the expression of CYP1A1 and inflammation-related genes, and to activate intracellular signalling pathways, in human bronchial epithelial cells. We specifically investigated to what extent DEP-induced expression of interleukin (IL)-6, IL-8 and cyclooxygenase (COX)-2 was regulated differentially from DEP-induced expression of CYP1A1.</p> <p>Results</p> <p>The cytotoxicity of the DEPs was characterised by a marked time- and concentration-dependent increase in necrotic cells at 4 h and above 200 μg/ml (~ 30 μg/cm²). DEP-induced DNA-damage was only apparent at high concentrations (≥ 200 μg/ml). IL-6, IL-8 and COX-2 were the three most up-regulated genes by the DEPs in a screening of 20 selected inflammation-related genes. DEP-induced expression of CYP1A1 was detected at very low concentrations (0.025 μg/ml), compared to the expression of IL-6, IL-8 and COX-2 (50-100 μg/ml). A CYP1A1 inhibitor (α-naphthoflavone), nearly abolished the DEP-induced expression of IL-8 and COX-2. Of the investigated mitogen-activated protein kinases (MAPKs), the DEPs induced activation of p38. A p38 inhibitor (SB202190) strongly reduced DEP-induced expression of IL-6, IL-8 and COX-2, but only moderately affected the expression of CYP1A1. The DEPs also activated the nuclear factor-κB (NF-κB) pathway, and suppression by siRNA tended to reduce the DEP-induced expression of IL-8 and COX-2, but not CYP1A1.</p> <p>Conclusion</p> <p>The present study indicates that DEPs induce both CYP1A1 and pro-inflammatory responses in vitro, but via differential intracellular pathways. DEP-induced pro-inflammatory responses seem to occur via activation of NF-κB and p38 and are facilitated by CYP1A1. However, the DEP-induced CYP1A1 response does not seem to involve NF-κB and p38 activation. Notably, the present study also indicates that expression of CYP1A1 may represent a particular sensitive biomarker of DEP-exposure.</p

Meeting Report: National Workshops for the Communication of Air Pollution and Health Information: Summary of Four Workshops in Different Regions of Europe

AIRNET was a thematic network project (2002–2004) initiated to stimulate the interaction between researchers in air pollution and health in Europe. As part of AIRNET’s communication strategy, a standardized workshop model was developed to organize national meetings on air pollution and health (AIRNET network days). Emphasis was given to tailor the national workshop information and related activities to the specific needs of a wider range of stakeholders (e.g., policy makers, nongovernmental organizations, industry representatives). In this report we present an overview of the results of four workshops held in western, northern, central/eastern, and southern regions of Europe in 2004. Overall, workshop experiences indicated that by actively involving participants in the planning of each meeting, AIRNET helped create an event that addressed participants’ needs and interests. A wide range of communication formats used to discuss air pollution and health also helped stimulate active interaction among participants. Overall, the national workshops held by AIRNET offered a way to improve communication among the different stakeholders. Because a broad stakeholder involvement in decision making can positively affect the development of widely supported policies, such meetings should be continued for Europe and elsewhere

Wood smoke particles from different combustion phases induce similar pro-inflammatory effects in a co-culture of monocyte and pneumocyte cell lines

Background Exposure to particulate matter (PM) has been linked to several adverse cardiopulmonary effects, probably via biological mechanisms involving inflammation. The pro-inflammatory potential of PM depends on the particles’ physical and chemical characteristics, which again depend on the emitting source. Wood combustion is a major source of ambient air pollution in Northern countries during the winter season. The overall aim of this study was therefore to investigate cellular responses to wood smoke particles (WSPs) collected from different phases of the combustion cycle, and from combustion at different temperatures. Results WSPs from different phases of the combustion cycle induced very similar effects on pro-inflammatory mediator release, cytotoxicity and cell number, whereas WSPs from medium-temperature combustion were more cytotoxic than WSPs from high-temperature incomplete combustion. Furthermore, comparisons of effects induced by native WSPs with the corresponding organic extracts and washed particles revealed that the organic fraction was the most important determinant for the WSP-induced effects. However, the responses induced by the organic fraction could generally not be linked to the content of the measured polycyclic aromatic hydrocarbons (PAHs), suggesting that also other organic compounds were involved. Conclusion The toxicity of WSPs seems to a large extent to be determined by stove type and combustion conditions, rather than the phase of the combustion cycle. Notably, this toxicity seems to strongly depend on the organic fraction, and it is probably associated with organic components other than the commonly measured unsubstituted PAHs

Studies on Health Effects of Transport-Related Air Pollution

see attached full documentJRC.H.4-Transport and air qualit

The occurrence of polycyclic aromatic hydrocarbons and their derivatives and the proinflammatory potential of fractionated extracts of diesel exhaust and wood smoke particles

Exposure to combustion emissions, including diesel engine exhaust and wood smoke particles (DEPs and WSPs), has been associated with inflammatory responses. To investigate the possible role of polycyclic aromatic hydrocarbons (PAHs) and PAH-derivatives, the DEPs and WSPs methanol extracts were fractionated by solid phase extraction (SPE), and the fractions were analyzed for more than ~120 compounds. The pro-inflammatory effects of the fractionated extracts were characterized by exposure of bronchial epithelial lung cells (BEAS-2B). Both native DEPs and WSPs caused a concentration-dependent increase in IL-6 and IL-8 release and cytotoxicity. This is consistent with the finding of a rather similar total content of PAHs and PAH-derivatives. Yet, the samples differed in specific components, suggesting that different species contribute to the toxicological response in these two types of particles. The majority of the IL-6 release and cytotoxicity was induced upon exposure to the most polar (methanol) SPE fraction of extracts from both samples. In these fractions hydroxy-PAHs, carboxy-PAHs were observed along with nitro-amino-PAHs in DEP. However, the biological effects induced by the polar fractions could not be attributed only to the occurrence of PAH-derivatives. The present findings indicate a need for further characterization of organic extracts, beyond an extensive analysis of commonly suspected PAH and PAH-derivatives

Cell toxicity and oxidative potential of engine exhaust particles : impact of using particulate filter or biodiesel fuel blend

The link between emissions of vehicular particulate matter (PM) and adverse health effects is well established. However, the influence of new emission control technologies and fuel types on both PM emissions and health effects has been less well investigated. We examined the health impact of PM emissions from two vehicles equipped with or without a diesel particulate filter (DPF). Both vehicles were powered either with diesel (B0) or a 50% v/v biodiesel blend (B50). The DPF effectively decreased PM mass emissions (∼85%), whereas the fuel B50 without DPF lead to less reduction (∼50%). The hazard of PM per unit distance driven was decreased for the DPF-equipped vehicle as indicated by a reduced cytotoxicity, oxidative, and pro-inflammatory potential. This was not evident and even led to an increase when the hazard was expressed on a per unit of mass basis. In general, the PM oxidative potential was similar or reduced for the B50 compared to the B0 powered vehicle. However, the use of B50 resulted in increased cytotoxicity and IL-6 release in BEAS-2B cells irrespective of the expression metric. This study shows that PM mass reduction achieved by the use of B50 will not necessarily decrease the hazard of engine emissions, while the application of a DPF has a beneficial effect on both PM mass emission and PM hazard