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Comparison of the pro-oxidative and proinflammatory effects of organic diesel exhaust particle chemicals in bronchial epithelial cells and macrophages
- Source :
- Journal of immunology (Baltimore, Md. : 1950). 169(8)
- Publication Year :
- 2002
-
Abstract
- 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.
- Subjects :
- Antioxidant
medicine.medical_treatment
Immunology
Apoptosis
Bronchi
Oxidative phosphorylation
Respiratory Mucosa
Biology
medicine.disease_cause
Proinflammatory cytokine
Cell Line
Membrane Potentials
chemistry.chemical_compound
Necrosis
Macrophages, Alveolar
medicine
Tumor Cells, Cultured
Immunology and Allergy
Cytotoxic T cell
Humans
Particle Size
Polycyclic Aromatic Hydrocarbons
Cells, Cultured
Vehicle Emissions
Inflammation
Superoxide
Interleukin-8
JNK Mitogen-Activated Protein Kinases
Glutathione
Intracellular Membranes
Cell biology
Mitochondria
Heme oxygenase
Enzyme Activation
Oxidative Stress
chemistry
Mitogen-Activated Protein Kinases
Reactive Oxygen Species
Oxidation-Reduction
Oxidative stress
Subjects
Details
- ISSN :
- 00221767
- Volume :
- 169
- Issue :
- 8
- Database :
- OpenAIRE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Accession number :
- edsair.doi.dedup.....9156ba81bf2fbd8f29a25fce54a26d8f