| dc.description.abstract | Oral metal exposure has been associated with diverse adverse reactions, including neurotoxicity. We showed
previously that dentally applied metals activate dendritic cells (MoDC) via TLR4 (Ni, Co, Pd) and TLR3 (Au). It
is still unknown whether the low levels of dental metals reaching the brain can trigger local innate cells or
prime them to become more responsive.
Here we tested whether dentally applied metals (Cr, Fe, Co, Ni, Cu, Zn, Au, Hg) activate primary human microglia
in vitro and, as a model, monocytic THP-1-cells, in high non-toxic as well as near-physiological concentrations. In
addition the effects of ‘near-physiological’ metal exposure on endotoxin (LPS) responsiveness of these cells were
evaluated. IL-8 and IL-6 production after 24 h was used as read out.
In high, non-toxic concentrations all transition metals except Cr induced IL-8 and IL-6 production in microglia,
with Ni and Co providing the strongest stimulation. When using near-physiological doses (up to 10× the normal
plasma concentration), only Zn and Cu induced significant IL-8 production. Of note, the latter metals also markedly
potentiated LPS responsiveness of microglia and THP-1 cells.
In conclusion, transition metals activate microglia similar to MoDCs. In near-physiological concentrations Zn and
Cu are the most effective mediators of innate immune activation. A clear synergism between innate responses to
Zn/Cu and LPS was observed, shedding new light on the possible relation between oral metal exposure and
neurotoxicity. | en_US |
