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Mar 9 – 11, 2015
NH Laguna Palace Hotel
Europe/Rome timezone

Synergistic TLR4-dependent effects of titanium dioxide nanoparticles and LPS on the activation of murine macrophages

Mar 11, 2015, 4:48 PM
24m
Breakout 1 (NH Laguna Palace Hotel)

Breakout 1

NH Laguna Palace Hotel

Viale Ancona, n° 2 30172 Venice-Mestre, Italy Tel: +39 041 829 6111 Fax: +39 848 390 230
Parallel Session 6A:Toxicology and human health risks 6AToxicology and human health risks

Speaker

Massimiliano Bianchi (Department of Biomedical Biotechnological and Translational Sciences, University of Parma, Italy)

Description

Additional Authors: Enrico Bergamaschi Department of Clinical and Experimental Medicine, University of Parma, Italy [email protected] Abstract: Nanomaterials may bind bioactive environmental contaminants, such as bacterial endotoxins, thus potentially acting as carriers for toxicants. To investigate the functional implications of this interaction, we have investigated the inflammogenic response mediated by two preparations of TiO2 nanoparticles (NP), co-administered with lipopolysaccharide (LPS), in Raw264.7 murine macrophages. TiO2 NP synergized the effect of LPS on both Nos2 mRNA and Nos2 protein expression as well as on NO production. TiO2 NP also potentiated the LPS effects on Ptgs2 expression and cytokine secretion. NP uptake was reduced by the cytoskeletal drug cytochalasin B thus suppressing the synergy between TiO2 NP and LPS. Pre-treatment with the TLR4 inhibitors polymyxin B and CLI-095 abolished the synergistic effect that was also partially hampered by the inhibition of p38 but not of ERK1/2, MAPK. This findings suggest that TiO2 NP enhance macrophage activation by LPS via a TLR4-dependent mechanism that involves p38 and an intracellular site; other NP, such as polystyrene NP, show the same effects. Different NP may deliver bioactive molecules to target organs through a “Trojan Horse effect”, thus enhancing macrophage activation leading to increased inflammation and worsening inflammatory status. Supported by EU FP7 Project Sanowork (Grant NMP4-SL-2012-280716 )

Primary author

Massimiliano Bianchi (Department of Biomedical Biotechnological and Translational Sciences, University of Parma, Italy)

Co-author

Manfredi Allegri (Department of Biomedical Biotechnological and Translational Sciences, University of Parma, Italy)

Presentation materials