title: Dental metal-induced innate reactivity in keratinocytes.
abstract: Gold, nickel, copper and mercury, i.e. four metals frequently used in dental applications, were explored for their capacity to induce innate immune activation in keratinocytes (KC). Due to their anatomical location the latter epithelial cells are key in primary local irritative responses of skin and mucosa. Fresh foreskin-derived keratinocytes and skin and gingiva KC cell lines were studied for IL-8 release as a most sensitive parameter for NF-kB activation. First, we verified that viral-defense mediating TLR3 is a key innate immune receptor in both skin- and mucosa derived keratinocytes. Second, we found that, in line with our earlier finding that ionized gold can mimic viral dsRNA in triggering TLR3, gold is very effective in KC activation. It would appear that epithelial TLR3 can play a key role in both skin- and mucosa localized irritation reactivities to gold. Subsequently we found that not only gold, but also nickel, copper and mercury salts can activate innate immune reactivity in keratinocytes, although the pathways involved remain unclear. Although current alloys have been optimized for minimal leakage of metal ions, secondary factors such as mechanical friction and acidity may still facilitate such leakage. Subsequently, these metal ions may create local irritation, itching and swelling by triggering innate immune reactions, potentially also facilitating the development of metal specific adaptive immunity.
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands; Department of Biomedical Sciences and Prostodontics, 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 Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, The Netherlands.
authors.forename: Jeroen K
authors.initials: JK
authors.lastname: Buskermolen
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 Dermatology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands; Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam, University of Amsterdam and VU University Amsterdam, The Netherlands.
authors.forename: Susan
authors.initials: S
authors.lastname: Gibbs
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands.
authors.forename: B Mary E
authors.initials: BM
authors.lastname: von Blomberg
authors.affiliation: Department of Pathology, VU University Medical Center, Amsterdam, Amsterdam, The Netherlands. Electronic address: i.vanhoogstraten@vumc.nl.
authors.forename: Ingrid M W
authors.initials: IM
authors.lastname: van Hoogstraten
mesh_terms: D002478:Cells, Cultured; D003764:Dental Materials / Q000633:toxicity*; D006801:Humans; D007113:Immunity, Innate / Q000187:drug effects*; D015603:Keratinocytes / Q000276:immunology*; D008670:Metals / Q000633:toxicity*; D051196:Toll-Like Receptor 3 / Q000502:physiology
chemical_list: D003764:Dental Materials; D008670:Metals; C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3
keywords: Contact allergy; Copper; Gold; Innate immunity; Keratinocyte; Mercury; Nickel; TLR