Lina Gölz1, Stefan Bayer2, Ludger Keilig3, Andreas Jäger4, Helmut Stark2, Christoph Bourauel3, Werner Götz4, Stilla Frede5, Jochen Winter6, Dominik Kraus2. 1. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany. Electronic address: lgoelz@uni-bonn.de. 2. Department of Prosthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany. 3. Oral Technology, University of Bonn, Bonn, Germany. 4. Department of Orthodontics, Center of Dento-Maxillo-Facial Medicine, University of Bonn, Bonn, Germany. 5. Department of Anesthesiology and Intensive Care Medicine, University of Bonn, Bonn, Germany. 6. Oral Cell Biology Group, Department of Periodontology, Operative and Preventive Dentistry, University of Bonn, Bonn, Germany.
Abstract
OBJECTIVES: 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. SIGNIFICANCE: Our in vitro study implicated that Ni(II) has various modifying effects on IL-1β-induced inflammatory processes depending on the concentration.
OBJECTIVES: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. SIGNIFICANCE: Our in vitro study implicated that Ni(II) has various modifying effects on IL-1β-induced inflammatory processes depending on the concentration.
Authors: Rafael Velasco-Ibáñez; Edith Lara-Carrillo; Raúl Alberto Morales-Luckie; Elizabeth Teresita Romero-Guzmán; Víctor Hugo Toral-Rizo; Marius Ramírez-Cardona; Verónica García-Hernández; Carlo Eduardo Medina-Solís Journal: Sci Rep Date: 2020-12-17 Impact factor: 4.379