title: Possible implications of Ni(II) on oral IL-1β-induced inflammatory processes.
abstract: OBJECTIVE
  Nickel (Ni) is one of the main metal elements in orthodontic and prosthetic devices. Different effects of Ni are described ranging from an induction of local inflammation to allergy and cancerous/mutagenic properties. Inflammatory reactions are frequently observed in the oral cavity, but the interrelationship of Ni with those events is still unknown. Therefore, we focused on the impact of Ni on inflammation in vitro.
  
  
  METHODS
  In accordance to previous immersion tests of our lab, human gingival fibroblasts (HGFs) (n=6) were exposed to a pro-inflammatory environment using interleukin-1 beta (IL-1β) and additionally stimulated with different Ni(II) concentrations (400 and 4000ng/ml). At varying time points the expression of pro- and anti-inflammatory as well as matrix degeneration proteins, i.e. MMPs, were analyzed. Furthermore, proliferation assays, wound healing tests and the detection of NF-κB activation were conducted. Unstimulated HGFs served as control.
  
  
  RESULTS
  Our experiments showed that low clinical average Ni(II) levels did not alter pro-inflammatory cytokines significantly compared to control (p>0.05). Instead, a 10-fold higher dose up-regulated these mediators significantly in a time-dependent manner (p<0.01). This was even more pronounced combining both Ni(II) concentrations with an inflammatory condition (p<0.001), MMP expressions were in line with our findings (p<0.001). The mRNA data were supported by proliferation and wound closure assays (p<0.001). However, the combination of both stimuli induced contradictory results. Analyzing NF-κB activation revealed that our results may be in part attributed to NF-κB.
  
  
  CONCLUSIONS
  Our in vitro study implicated that Ni(II) has various modifying effects on IL-1β-induced inflammatory processes depending on the concentration.
authors.affiliation: Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany. Electronic address: lgoelz@uni-bonn.de.
authors.forename: Lina
authors.initials: L
authors.lastname: Gölz
authors.affiliation: Department of Prosthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bayer
authors.affiliation: Oral Technology, University of Bonn, Bonn, Germany.
authors.forename: Ludger
authors.initials: L
authors.lastname: Keilig
authors.affiliation: Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jäger
authors.affiliation: Department of Prosthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Stark
authors.affiliation: Oral Technology, University of Bonn, Bonn, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Bourauel
authors.affiliation: Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: Werner
authors.initials: W
authors.lastname: Götz
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany.
authors.forename: Stilla
authors.initials: S
authors.lastname: Frede
authors.affiliation: Oral Cell Biology Group, Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.
authors.forename: Jochen
authors.initials: J
authors.lastname: Winter
authors.affiliation: Department of Prosthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Kraus
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000276:immunology; D018929:Cell Culture Techniques; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005347:Fibroblasts / Q000187:drug effects / Q000276:immunology*; D005881:Gingiva / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000276:immunology; D018836:Inflammation Mediators / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology; D053583:Interleukin-1beta / Q000276:immunology*; D016209:Interleukin-8 / Q000187:drug effects / Q000276:immunology; D008422:Materials Testing; D020781:Matrix Metalloproteinase 1 / Q000187:drug effects / Q000276:immunology; D020784:Matrix Metalloproteinase 8 / Q000187:drug effects / Q000276:immunology; D016328:NF-kappa B / Q000187:drug effects / Q000276:immunology; D009532:Nickel / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D053773:Transforming Growth Factor beta1 / Q000187:drug effects / Q000276:immunology; D055815:Young Adult
chemical_list: D000893:Anti-Inflammatory Agents; C508606:CXCL8 protein, human; C508609:IL10 protein, human; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D016328:NF-kappa B; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10; D009532:Nickel; C488762:MMP8 protein, human; D020784:Matrix Metalloproteinase 8; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Biocompatibility; Cell proliferation; Dental alloy; Gingival fibroblasts; IL-1β; Inflammation; MMPs; NF-κB; Nickel; Wound healing