Regulation of isocyanate-induced apoptosis, oxidative stress, and inflammation in cultured human neutrophils: isocyanate-induced neutrophils apoptosis
| Autor: | Pradyumna Kumar Mishra, Subodh Kumar Jain, Saba Khan, Kewal K. Maudar, Hariom Panwar, Smita Banerjee, Arpit Bhargava |
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| Rok vydání: | 2008 |
| Předmět: |
Neutrophils
Health Toxicology and Mutagenesis medicine.medical_treatment Glutathione reductase Apoptosis DNA Fragmentation Toxicology medicine.disease_cause chemistry.chemical_compound medicine Deoxyguanosine Humans Cells Cultured chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species Caspase 3 Cell Biology Isocyanate Molecular biology Oxidative Stress Cytokine Glutathione Reductase Biochemistry chemistry Cytokines Tumor necrosis factor alpha Environmental Pollutants Inflammation Mediators Reactive Oxygen Species Oxidative stress Isocyanates |
| Zdroj: | Cell biology and toxicology. 26(3) |
| ISSN: | 1573-6822 |
| Popis: | Implications of environmental toxins on the regulation of neutrophil function are being significantly appraised. Such effects can be varied and markedly different depending on the type and extent of chemical exposure, which results in direct damage to the immune system. Isocyanates with functional group (-NCO), are considered as highly reactive molecules with diverse industrial applications. However, patho-physiological implications resulting from their occupational and accidental exposures have not been well delineated. The present study was carried out to assess the immunotoxic response of isocyanates and their mode of action at a molecular level on cultured human neutrophils isolated from healthy human volunteers. Studies were conducted to evaluate both dose- and time-dependent (n = 3) response using N-succinimidyl N-methylcarbamate, a chemical entity that mimics the effects of methyl isocyanate in vitro. Measure of apoptosis through annexin-V-FITC/PI assay, active caspase-3, apoptotic DNA ladder assay and mitochondrial depolarization; induction of oxidative stress by CM-H(2)DCFDA and formation of 8'-hydroxy-2'-deoxyguanosine; and levels of antioxidant defense system enzyme glutathione reductase, multiplex cytometric bead array analysis to quantify the secreted cytokine levels (interleukin-8, interleukin-1beta, interleukin-6, interleukin-10, interferon-gamma, tumor necrosis factor, and interleukin-12p70) parameters were evaluated. Our results demonstrate that isocyanates induce neutrophil apoptosis via activation of mitochondrial-mediated pathway along with reactive oxygen species production; depletion in antioxidant defense states; and elevated pro-inflammatory cytokine response. |
| Databáze: | OpenAIRE |
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