Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E2 synthesis: In vitro and in vivo studies
Open Access
- 22 December 2009
- journal article
- Published by Springer Science and Business Media LLC in Particle and Fibre Toxicology
- Vol. 6 (1), 34
- https://doi.org/10.1186/1743-8977-6-34
Abstract
Ambient particulate matter (PM)-associated metals have been shown to play an important role in cardiopulmonary health outcomes. To study the modulation of PM-induced inflammation by leached off metals, we investigated intracellular solubility of radio-labeled iron oxide (59Fe2O3) particles of 0.5 and 1.5 μm geometric mean diameter. Fe2O3 particles were examined for the induction of the release of interleukin 6 (IL-6) as pro-inflammatory and prostaglandin E2 (PGE2) as anti-inflammatory markers in cultured alveolar macrophages (AM) from Wistar Kyoto (WKY) rats. In addition, we exposed male WKY rats to monodispersed Fe2O3 particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight) to examine in vivo inflammation. Particles of both sizes are insoluble extracellularly in the media but moderately soluble in AM with an intracellular dissolution rate of 0.0037 ± 0.0014 d-1 for 0.5 μm and 0.0016 ± 0.0012 d-1 for 1.5 μm 59Fe2O3 particles. AM exposed in vitro to 1.5 μm particles (10 μg/mL) for 24 h increased IL-6 release (1.8-fold; p < 0.05) and also PGE2 synthesis (1.9-fold; p < 0.01). By contrast, 0.5 μm particles did not enhance IL-6 release but strongly increased PGE2 synthesis (2.5-fold, p < 0.005). Inhibition of PGE2 synthesis by indomethacin caused a pro-inflammatory phenotype as noted by increased IL-6 release from AM exposed to 0.5 μm particles (up to 3-fold; p < 0.005). In the rat lungs, 1.5 but not 0.5 μm particles (4.0 mg/kg) induced neutrophil influx and increased vascular permeability. Fe2O3 particle-induced neutrophilic inflammatory response in vivo and pro-inflammatory cytokine release in vitro might be modulated by intracellular soluble iron via PGE2 synthesis. The suppressive effect of intracellular released soluble iron on particle-induced inflammation has implications on how ambient PM-associated but soluble metals influence pulmonary toxicity of ambient PM.Keywords
This publication has 38 references indexed in Scilit:
- Particokinetics and Extrapulmonary Translocation of Intratracheally Instilled Ferric Oxide Nanoparticles in Rats and the Potential Health Risk AssessmentToxicological Sciences, 2008
- Iron-regulatory proteins: molecular biology and pathophysiological implicationsExpert Reviews in Molecular Medicine, 2007
- Particulate matter in the environment: pulmonary and cardiovascular effectsCurrent Opinion in Pulmonary Medicine, 2007
- Alveolar macrophage cytokine response to air pollution particles: Oxidant mechanismsToxicology and Applied Pharmacology, 2006
- Redox signaling: Bioinorganic chemistry at its bestJournal of Inorganic Biochemistry, 2006
- CARDIAC AND THERMOREGULATORY EFFECTS OF INSTILLED PARTICULATE MATTER-ASSOCIATED TRANSITION METALS IN HEALTHY AND CARDIOPULMONARY-COMPROMISED RATSJournal of Toxicology and Environmental Health, Part A, 2002
- Agglomerates of Ultrafine Particles of Elemental Carbon and TiO 2 Induce Generation of Lipid Mediators in Alveolar MacrophagesEnvironmental Health Perspectives, 2001
- Agglomerates of ultrafine particles of elemental carbon and TiO2 induce generation of lipid mediators in alveolar macrophages.Environmental Health Perspectives, 2001
- Epidemiologic evidence of cardiovascular effects of particulate air pollution.Environmental Health Perspectives, 2001
- An interspecies comparison of the lung clearance of inhaled monodisperse cobalt oxide particles—Part I: Objectives and summary of resultsJournal of Aerosol Science, 1989