TY  - EJOU
AU  - Lucarelli, Marilena 
AU  - Gatti, Antonietta M. 
AU  - Savarino, Graziana 
AU  - Quattroni, Paola 
AU  - Martinelli, Lucia 
AU  - Monari, Emanuela 
AU  - Boraschi, Diana 

TI  - Innate defence functions of macrophages can be biased by nano-sized ceramic and metallic particles
T2  - European Cytokine Network

PY  - 2004
VL  - 15
IS  - 4
SN  - 1952-4005

AB  - Nano-sized particles of ceramic and metallic materials are generated by high-tech industrial
activities, and can be generated from worn-out replacement and prosthetic implants. The interaction with the
human body of such nanoparticles has been investigated, with a particular emphasis on innate defence
mechanisms. Human macrophages (PMA-differentiated myelomonocytic U-937 cells) were exposed in vitro to
non-toxic concentrations of TiO<sub>2</sub>, SiO<sub>2</sub>, ZrO<sub>2</sub>, or Co nanoparticles, and their inflammatory response (expression
of TLR receptors and co-receptors, and cytokine production) was examined. Expression of TLR receptors was
generally unaffected by exposure to the different nanoparticles, except for some notable cases. Exposure to
nanoparticles of ZrO<sub>2</sub> (and to a lesser extent TiO<sub>2</sub>), upregulated expression of viral TLR receptors TLR3 and
TLR7. Expression of TLR10 was also increased by TiO<sub>2</sub> and ZrO<sub>2</sub> nanoparticles. On the other hand, TLR9
expression was decreased by SiO<sub>2</sub> nano-particles, and expression of the co-receptor CD14 was inhibited by Co
nanoparticles. Basal and LPS-induced production of cytokines IL-1β, TNF-α, and IL-1Ra was examined in
macrophages exposed to nanoparticles. SiO<sub>2</sub> nanoparticles strongly biased naïve macrophages towards inflam-mation
(M1 polarisation), by selectively inducing production of inflammatory cytokines IL-1β and TNF-α. SiO<sub>2</sub>
nanoparticles also significantly amplified the inflammatory phenotype of LPS-polarised M1 macrophages. Other
ceramic nanoparticles had little influence on cytokine production, either in resting macrophages, or in
LPS-activated cells. Generally, Co nanoparticles had an overall pro-inflammatory effect on naïve macrophages,
by reducing anti-inflammatory IL-1Ra and inducing inflammatory TNF-α. However, Co nanoparticles reduced
production of IL-1β and IL-1Ra, but not TNF-α, in LPS-polarised M1 macrophages. Thus, exposure to different
nanoparticles can modulate, in different ways, the defence/inflammatory capacities of macrophages. A thorough
analysis of these biasing effects may shed light on the mechanisms of pathogensis of several diseases based on
dysregulation of the immune response (allergies, autoimmunity, tumours).
KW  - nanoparticles
KW  -  inflammation
KW  -  macrophages
KW  -  TLR receptors
KW  -  cytokines
KW  -  innate immunity

DO  -