Cytokine Production by Human Airway Epithelial Cells after Exposure to an Air Pollution Particle Is Metal-Dependent

• Published in: Toxicology and applied pharmacology 1997-10, Vol.146 (2), p.180-188
• Main Authors: Carter, Jacqueline D., Ghio, Andrew J., Samet, James M., Devlin, Robert B.
• Format: Article
• Language: English
• Subjects: Air; Air Pollutants, Occupational - adverse effects; Biological and medical sciences; Bronchi - drug effects; Bronchi - metabolism; Carbon - adverse effects; Cells, Cultured; Chelating Agents - pharmacology; Coal Ash; Cytokines - biosynthesis; Cytokines - genetics; Deferoxamine - pharmacology; Environmental pollutants toxicology; Epithelial Cells - drug effects; Epithelial Cells - metabolism; Free Radical Scavengers - pharmacology; Humans; Interleukin-6 - biosynthesis; Interleukin-6 - genetics; Interleukin-8 - biosynthesis; Interleukin-8 - genetics; Iron - adverse effects; Medical sciences; Metals - adverse effects; Nickel - adverse effects; Particle Size; Particulate Matter; RNA, Messenger - analysis; RNA, Messenger - genetics; Thiourea - analogs & derivatives; Thiourea - pharmacology; Toxicology; Tumor Necrosis Factor-alpha - biosynthesis; Tumor Necrosis Factor-alpha - genetics; Vanadium - adverse effects
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1006/taap.1997.8254

Despite the many epidemiological studies supporting the contention that ambient air pollution particles can adversely affect human health, there is no clear agreement as to a biologically plausible mechanism which can explain the acute mortality and morbidity associated with exposure to particles less than 10 μm in size. We tested the hypothesis that metals present in an air pollution particle can induce the synthesis and expression of the inflammatory cytokines IL-8, IL-6, and TNFα. A residual oil fly ash (ROFA) containing the transition metals vanadium, nickel, and iron was used as a model emission source air pollution particle. Normal human bronchial epithelial (NHBE) cells were exposed for either 2 or 24 hr to 0, 5, 50, or 200 μg/ml ROFA. Concentrations of IL-8, IL-6, and TNF-α proteins were measured with commercially available ELISA kits. mRNA for these same cytokines was quantified by RT-PCR. NHBE cells exposed to ROFA produced significant amounts of IL-8, IL-6, and TNF, as well as mRNAs coding for these cytokines. Cytokine production was inhibited by the inclusion of either the metal chelator deferoxamine (1.0 mm) or the free radical scavenger dimethylthiourea (1.0 mm). In addition, vanadium containing compounds, but not iron or nickel sulfates, mimicked the effects of intact ROFA. These results demonstrate that metals present in ROFA may be responsible for production and release of inflammatory mediators by the respiratory tract epithelium and suggest that these mediators may contribute to the toxic effects of particulate air pollutants reported in epidemiology studies.