| dc.description.abstract | Nickel, cobalt and palladium ions can induce an innate immune response by triggering Toll-like receptor
(TLR)-4 which is present on dendritic cells (DC). Here we studied mechanisms of action for DC immunotoxicity
to gold and mercury. Next to gold (Na
3
Au (S
2
O
3
)
2
2H
2
O) and mercury (HgCl
) was
included as a positive control. MoDC activation was assessed by release of the pro-inflammatory mediator
IL-8. Also PBMC were studied, and THP-1 cells were used as a substitution for DC for evaluation
of cytokines and chemokines, as well as phenotypic, alterations in response to gold and mercury. Our
results showed that both Na
3
Au (S
2
O
3
)
2
2H
2
O and HgCl
induce substantial release of IL-8, but not IL6,
CCL2 or IL-10, from MoDc, PBMC, or THP-1 cells. Also gold and, to a lesser extent mercury, caused modest
dendritic cell maturation as detected by increased membrane expression of CD40 and CD80. Both
metals thus show innate immune response capacities, although to a lower extent than reported earlier
for NiCl
2
, CoCl
2
and Na
2
[PdCl
4
2
]. Importantly, the gold-induced response could be ascribed to TLR3 rather
than TLR4 triggering, whereas the nature of the innate mercury response remains to be clarified. In conclusion
both gold and mercury can induce innate immune responses, which for gold could be ascribed to
TLR3 dependent signalling. These responses are likely to contribute to adaptive immune responses to
these metals, as reflected by skin and mucosal allergies. | en_US |
