title: Innate stimulatory capacity of high molecular weight transition metals Au (gold) and Hg (mercury).
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 (Na3Au (S2O3)2⋅2H2O) and mercury (HgCl2), nickel (NiCl2) 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 Na3Au (S2O3)2⋅2H2O and HgCl2 induce substantial release of IL-8, but not IL-6, 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 NiCl2, CoCl2 and Na2 [PdCl4]. 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.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands; Department of Biomedical Science and Dept of Prosthodontic, Faculty of Dentistry, Jember University, Indonesia. Electronic address: D.rachmawati@unej.ac.id.
authors.forename: Dessy
authors.initials: D
authors.lastname: Rachmawati
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Inás W A
authors.initials: IW
authors.lastname: Alsalem
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Hetty J
authors.initials: HJ
authors.lastname: Bontkes
authors.affiliation: Department of Molecular Cell Biology, Medical Faculty, VU University Amsterdam, The Netherlands.
authors.forename: Marleen I
authors.initials: MI
authors.lastname: Verstege
authors.affiliation: Department of Dermatology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sue
authors.initials: S
authors.lastname: Gibbs
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: B M E
authors.initials: BM
authors.lastname: von Blomberg
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Rik J
authors.initials: RJ
authors.lastname: Scheper
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ingrid M W
authors.initials: IM
authors.lastname: van Hoogstraten
mesh_terms: D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006046:Gold / Q000737:chemistry / Q000633:toxicity*; D057809:HEK293 Cells; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D008628:Mercury / Q000737:chemistry / Q000633:toxicity*; D008970:Molecular Weight; D051195:Toll-Like Receptor 2 / Q000378:metabolism; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000378:metabolism
chemical_list: D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D006046:Gold; D008628:Mercury
keywords: Contact allergy; Dendritic cells; Gold; Innate immunity; Mercury; TLR3