Chemical and biological characterization of organic material from gasoline exhaust particles

Alsberg, Tomas; Stenberg, Ulf; Westerholm, Roger; Strandell, Michael; Rannug, Ulf; Sundvall, Annica; Romert, Lennart; Bernson, Vibeke S. M.; Pettersson, Bertil

doi:10.1021/es00131a003

Cited by 144 publications

(83 citation statements)

References 19 publications

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“…DEP contain a host of organic chemicals, among which the aliphatic hydrocarbons, heterocyclic compounds, aromatic hydrocarbons (e.g., PAH), and polar compounds (e.g., quinones) constitute the major groups (52)(53)(54)(55). Previous studies have demonstrated that the polar and, to a lesser extent, the aromatic fractions are inducers of HO-1 expression in RAW 264.7 cells (26).…”

Section: Establishment Of a Stable Transfected Cell Line To Test The mentioning

confidence: 99%

Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals

Alam

Venkatesan

et al. 2004

The Journal of Immunology

416

340

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The proinflammatory effects of particulate pollutants, including diesel exhaust particles (DEP), are related to their content of redox cycling chemicals and their ability to generate oxidative stress in the respiratory tract. An antioxidant defense pathway, which involves phase II enzyme expression, protects against the pro-oxidative and proinflammatory effects of DEP. The expression of enzymes, including heme oxygenase-1 (HO-1) and GST, is dependent on the activity of a genetic antioxidant response element in their promoters. In this study we investigated the mechanism by which redox cycling organic chemicals, prepared from DEP, induce phase II enzyme expression as a protective response. We demonstrate that aromatic and polar DEP fractions, which are enriched in polycyclic aromatic hydrocarbons and quinones, respectively, induce the expression of HO-1, GST, and other phase II enzymes in macrophages and epithelial cells. We show that HO-1 expression is mediated through accumulation of the bZIP transcription factor, Nrf2, in the nucleus, and that Nrf2 gene targeting significantly weakens this response. Nrf2 accumulation and subsequent activation of the antioxidant response element is regulated by the proteasomal degradation of Nrf2. This pathway is sensitive to pro-oxidative and electrophilic DEP chemicals and is also activated by ambient ultrafine particles. We propose that Nrf2-mediated phase II enzyme expression protects against the proinflammatory effects of particulate pollutants in the setting of allergic inflammation and asthma.

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Section: Establishment Of a Stable Transfected Cell Line To Test The mentioning

confidence: 99%

Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals

Alam

Venkatesan

et al. 2004

The Journal of Immunology

416

340

View full text Add to dashboard Cite

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“…Pollutants released from industry, 1) diesel and gasoline engines, 2,3) incineration, 4) home heating 5) and other activities, consist of complex chemical components, among them, potential and proven mutagens and carcinogens. 6,7) These complex chemical components might interact.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of Airborne Particulates Sampled Roadside in Rodent and Human Lung Fibroblasts.

Yamaguchi

Yamazaki

2001

JOURNAL OF HEALTH SCIENCE

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The number of diesel-powered vehicles has been increasing in Japan in recent years. And chronic exposure to relatively low levels of diesel exhaust may be a risk factor for respiratory diseases. It has been demonstrated that the airborne particulates sampled at a roadside contain exhaust from diesel engines. The present study has been undertaken to evaluate the cytotoxicity of airborne particulates in human and Chinese hamster lung fibroblast cell lines (WI-38 and CHL/IU). Conversion of mitochondrial MTS, leakage of lactate dehydrogenase (LDH), and the effect on cell proliferation curves were monitored. A dose-related effect of airborne particulate extracts was observed in MTS and LDH leakage assay with both cell lines. Crude extract was most cytotoxic in the MTS assay and had a significant effect on cell proliferation. The response of extracts and fractions of these extracts on MTS assay were similar to the effect on cell proliferation in both cell systems. An increase in LDH leakage was detected in all extracts and fractions except crude extract. In comparison, CHL/IU proved to be more sensitive than WI-38 in MTS assay, but most extracts and fractions were more toxic to WI-38 in LDH leakage assay. These results suggest that even a small amount of substances in airborne particulates was toxic to both cell systems.

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“…Macrophages constitute an important target for DEP in the lung (17,18,(21)(22)(23). After phagocytosis of these particles, macrophages respond in a hierarchical fashion to increasing particle load and incremental levels of oxidative stress (24).…”

mentioning

confidence: 99%

Comparison of the Pro-Oxidative and Proinflammatory Effects of Organic Diesel Exhaust Particle Chemicals in Bronchial Epithelial Cells and Macrophages

Wang

Oberley

et al. 2002

The Journal of Immunology

288

231

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Inhaled diesel exhaust particles (DEP) exert proinflammatory effects in the respiratory tract. This effect is related to the particle content of redox cycling chemicals and is involved in the adjuvant effects of DEP in atopic sensitization. We demonstrate that organic chemicals extracted from DEP induce oxidative stress in normal and transformed bronchial epithelial cells, leading to the expression of heme oxygenase 1, activation of the c-Jun N-terminal kinase cascade, IL-8 production, as well as induction of cytotoxicity. Among these effects, heme oxygenase 1 expression is the most sensitive marker for oxidative stress, while c-Jun N-terminal kinase activation and induction of apoptosis-necrosis require incremental amounts of the organic chemicals and increased levels of oxidative stress. While a macrophage cell line (THP-1) responded in similar fashion, epithelial cells produced more superoxide radicals and were more susceptible to cytotoxic effects than macrophages. Cytotoxicity is the result of mitochondrial damage, which manifests as ultramicroscopic changes in organelle morphology, a decrease in the mitochondrial membrane potential, superoxide production, and ATP depletion. Epithelial cells also differ from macrophages in not being protected by a thiol antioxidant, N-acetylcysteine, which effectively protects macrophages against cytotoxic DEP chemicals. These findings show that epithelial cells exhibit a hierarchical oxidative stress response that differs from that of macrophages by more rapid transition from cytoprotective to cytotoxic responses. Moreover, epithelial cells are not able to convert N-acetylcysteine to cytoprotective glutathione.

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Chemical and biological characterization of organic material from gasoline exhaust particles

Cited by 144 publications

References 19 publications

Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals

Nrf2 Is a Key Transcription Factor That Regulates Antioxidant Defense in Macrophages and Epithelial Cells: Protecting against the Proinflammatory and Oxidizing Effects of Diesel Exhaust Chemicals

Cytotoxicity of Airborne Particulates Sampled Roadside in Rodent and Human Lung Fibroblasts.

Comparison of the Pro-Oxidative and Proinflammatory Effects of Organic Diesel Exhaust Particle Chemicals in Bronchial Epithelial Cells and Macrophages

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