title: Role of soluble metals in oil fly ash-induced airway epithelial injury and cytokine gene expression.
abstract: Particulate matter (PM) metal content and bioavailability have been hypothesized to play a role in the health effects epidemiologically associated with PM exposure, in particular that associated with emission source PM. Using rat tracheal epithelial cells in primary culture, the present study compared and contrasted the acute airway epithelial effects of an emission source particle, residual oil fly ash (ROFA), with that of its principal constitutive transition metals, namely iron, nickel, and vanadium. Over a 24-h period, exposure to ROFA, vanadium, or nickel plus vanadium, but not to iron or nickel, resulted in increased epithelial permeability, decreased cellular glutathione, cell detachment, and lytic cell injury. Treatment of vanadium-exposed cells with buthionine sulfoximine further increased cytotoxicity. Conversely, treatment with the radical scavenger dimethylthiourea inhibited the effects in a dose-dependent manner. RT-PCR analysis of RNA isolated from ROFA-exposed rat tracheal epithelial cells demonstrated significant macrophage inflammatory protein-2 and interleukin-6 gene expression as early as 6 h after exposure, whereas gene expression of inducible nitric oxide synthase was maximally increased 24 h postexposure. Again, vanadium (not nickel) appeared to be mediating the effects of ROFA on gene expression. Treatment with dimethylthiourea inhibited both ROFA- and vanadium-induced gene expression in a dose-dependent manner. Corresponding effects were observed in interleukin-6 and macrophage inflammatory protein-2 synthesis. In summary, generation of an oxidative stress was critical to induction of the ROFA- or vanadium-induced effects on airway epithelial gene expression, cytokine production, and cytotoxicity.
authors.affiliation: National Health and Environmental Effects Research Laboratory, Experimental Toxicology Division, Pulmonary Toxicology Branch, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Dye
authors.forename: K B
authors.initials: KB
authors.lastname: Adler
authors.forename: J H
authors.initials: JH
authors.lastname: Richards
authors.forename: K L
authors.initials: KL
authors.lastname: Dreher
mesh_terms: D000818:Animals; D002244:Carbon / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D054426:Chemokine CXCL2; D060729:Coal Ash; D016207:Cytokines / Q000235:genetics*; D004847:Epithelial Cells / Q000187:drug effects / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000235:genetics; D008297:Male; D008670:Metals / Q000494:pharmacology*; D015846:Monokines / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052638:Particulate Matter; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D014132:Trachea / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology
chemical_list: D054426:Chemokine CXCL2; D060729:Coal Ash; D016207:Cytokines; D015850:Interleukin-6; D008670:Metals; D015846:Monokines; D052638:Particulate Matter; D002244:Carbon; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat