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

Division of Clinical Immunology and Allergy, Department of Medicine, University of California-Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA.
The Journal of Immunology (Impact Factor: 4.92). 11/2002; 169(8):4531-41. DOI: 10.4049/jimmunol.169.8.4531
Source: PubMed


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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    • "After the particles or pathogens have eluded or overwhelmed the epithelial barrier of the upper airways, they come into contact with the dedicated antigen presenting dendritic cells (DCs) (e.g. Steinman and Cohn, 1973; Nicod, 1997; Lipscomb and Masten, 2002; Holt, 2005) which are highly phagocytic (Dreher et al., 2001; Kiama et al., 2001, 2006; Walter et al., 2001). If they reach the alveolar surface, they are dealt with by the PSMs (e.g. "

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    • "While activation of p38 MAPK was analyzed 2 and 4 h after the addition of OE, COX-2 protein was determined at the 16-h time point [16] [21] [27]. Cell lysate preparation, protein assay and western blot were performed as previously described [15] [27] [28]. HO-1, phosphorylated p38, total p38, COX- 2, and ␤-actin proteins were detected using respective primary Abs (1:1000) followed by horseradish peroxidaseconjugated secondary Abs (1:1000). "
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    ABSTRACT: Commercial charbroiling emissions are a significant source of ambient particulate matter (PM) in urban settings. The objective of this study was to determine whether organic extract of PM emissions from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells and whether this effect was mediated by oxidative stress. PM samples were collected during cooking hamburgers on a commercial-grade under-fired charbroiler and sequentially extracted with water and methanol to obtain the aqueous PM suspension (AqPM) and organic extract (OE). The pro-oxidative and pro-inflammatory effects of OE were assessed using human bronchial epithelial cell line BEAS-2B. While AqPM did not have any effect, OE effectively induced the expression of heme oxygennase-1 and cyclooxygenase-2 in BEAS-2B cells. OE also up-regulated the levels of IL-6, IL-8, and prostaglandin E2. OE-induced cellular inflammatory response could be effectively suppressed by the antioxidant N-acetyl cysteine, nuclear factor (erythroid-derived 2)-like 2 activator sulforaphane and p38 MAPK inhibitor SB203580. In conclusion, organic chemicals emitted from commercial charbroiling meat operations could induce an inflammatory response in human bronchial epithelial cells, which was mediated by oxidative stress and p38 MAPK.
    Toxicology Reports 12/2014; 1. DOI:10.1016/j.toxrep.2014.09.015
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    • "ular stress response pathways . Cellular stress response hierarchies have been linked to induction of differing gene clusters depending upon the level and type of agent applied [ Li et al . , 2002a ; Benton et al . , 2006 ; de Graaf et al . , 2009 ; Woods et al . , 2009 ] and the tissue / cell type under investigation [ Toussaint et al . , 2000b ; Li et al . , 2002b ; Murray et al . , 2004 ] . Among the three distinct phenotypes of surviving cell clones detected in the SRR assay , only Phenotype - Hprt / HPRT — clones have been evaluated frequently as bio - markers for quantitative investigation of environmental agent - induced effects [ Albertini and Hayes , 1997 ; Albertini et al . , 2010 ] . Mut"
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    ABSTRACT: The events or factors that lead from normal cell function to conditions and diseases such as aging or cancer reflect complex interactions between cells and their environment. Cellular stress responses, a group of processes involved in homeostasis and adaptation to environmental change, contribute to cell survival under stress and can be resolved with damage avoidance or damage tolerance outcomes. To investigate the impact of environmental agents/conditions upon cellular stress response outcomes in epithelium, a novel quantitative assay, the "stress response resolution" (SRR) assay, was developed. The SRR assay consists of pretreatment with a test agent or vehicle followed later by a calibrated stress conditions exposure step (here, using 6-thioguanine). Pilot studies conducted with a spontaneously-immortalized murine mammary epithelial cell line pretreated with vehicle or 20 µg N-ethyl-N-nitrososurea/ml medium for 1 hr, or two hTERT-immortalized human bronchial epithelial cell lines pretreated with vehicle or 100 µM zidovudine/lamivudine for 12 days, found minimal alterations in cell morphology, survival, or cell function through 2 weeks post-exposure. However, when these pretreatments were followed 2 weeks later by exposure to calibrated stress conditions of limited duration (for 4 days), significant alterations in stress resolution were observed in pretreated cells compared with vehicle-treated control cells, with decreased damage avoidance survival outcomes in all cell lines and increased damage tolerance outcomes in two of three cell lines. These pilot study results suggest that sub-cytotoxic pretreatments with chemical mutagens have long-term adverse impact upon the ability of cells to resolve subsequent exposure to environmental stressors. Environ. Mol. Mutagen. 00:000-000, 2013. © 2013 Wiley Periodicals, Inc.
    Environmental and Molecular Mutagenesis 05/2013; 54(4). DOI:10.1002/em.21772 · 2.63 Impact Factor
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