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Beck-Speier, I. ; Kreyling, W.G. ; Maier, K.L. ; Dayal, N. ; Schladweiler, M.C.* ; Mayer, P. ; Semmler-Behnke, M. ; Kodavanti, U.P.*

Soluble iron modulates iron oxide particle-induced inflammatory responses via prostaglandin E₂ synthesis: In vitro and in vivo studies.

Part. Fibre Toxicol. 6:34 (2009)
Verlagsversion Volltext DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
BACKGROUND: 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 ((59)Fe(2)O(3)) particles of 0.5 and 1.5 mum geometric mean diameter. Fe(2)O(3 )particles were examined for the induction of the release of interleukin 6 (IL-6) as pro-inflammatory and prostaglandin E(2 )(PGE(2)) as anti-inflammatory markers in cultured alveolar macrophages (AM) from Wistar Kyoto (WKY) rats. In addition, we exposed male WKY rats to monodispersed Fe(2)O(3 )particles by intratracheal instillation (1.3 or 4.0 mg/kg body weight) to examine in vivo inflammation. RESULTS: 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 mum and 0.0016 +/- 0.0012 d(-1 )for 1.5 mum (59)Fe(2)O(3 )particles. AM exposed in vitro to 1.5 mum particles (10 mug/mL) for 24 h increased IL-6 release (1.8-fold; p < 0.05) and also PGE(2 )synthesis (1.9-fold; p < 0.01). By contrast, 0.5 mum particles did not enhance IL-6 release but strongly increased PGE(2 )synthesis (2.5-fold, p < 0.005). Inhibition of PGE(2 )synthesis by indomethacin caused a pro-inflammatory phenotype as noted by increased IL-6 release from AM exposed to 0.5 mum particles (up to 3-fold; p < 0.005). In the rat lungs, 1.5 but not 0.5 mum particles (4.0 mg/kg) induced neutrophil influx and increased vascular permeability. CONCLUSIONS: Fe(2)O(3 )particle-induced neutrophilic inflammatory response in vivo and pro-inflammatory cytokine release in vitro might be modulated by intracellular soluble iron via PGE(2 )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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter OIL FLY-ASH; AMBIENT PARTICULATE MATTER; ALVEOLAR MACROPHAGES; LUNG CLEARANCE; FERRIC-OXIDE; PULMONARY RESPONSES; ULTRAFINE PARTICLES; LIPID MEDIATORS; RATS; TRANSLOCATION
ISSN (print) / ISBN 1743-8977
e-ISSN 1743-8977
Zeitschrift Particle and Fibre Toxicology
Quellenangaben Band: 6, Heft: , Seiten: , Artikelnummer: 34 Supplement: ,
Verlag BioMed Central
Verlagsort London
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Lung Health and Immunity (LHI)