Ni(II) alters the NFκB signaling pathway in monocytic cells.

Nickel-based alloys are used for dental restorations because of their strength, high moduli, and relatively low cost. However, these alloys corrode significantly in use, particularly in lower pH environments that are common under oral biofilms. Ni(II) corrosion products increase inflammatory cytokine secretion from activated monocytes, suggesting that nickel alloys may exacerbate inflammatory responses in adjacent periodontal tissues caused by dental plaque. Because inflammatory cytokine secretion is regulated in part by the NFκB signaling pathway, our goal in the current work was to determine whether Ni(II) altered cellular levels or nuclear localization of NFκB-family subtypes. THP1 monocytes were exposed to Ni(II) for 72 h, and activated with lipopolysaccharide for the last 30 min to 6 h. Secretion of IL6 and TNFα were measured using ELISA, and NFκB levels and localization was measured using SDS-PAGE with immunoblots and digital analysis. We observed that Ni(II) did not alter the levels of secreted TNFα from activated monocytes, but increased secreted IL6 levels about 30% over controls. Ni(II) did not alter whole-cell levels of any NFκB subtype, but increased nuclear persistance of p65 and c-Rel. Our results suggest that Ni(II) may increase inflammatory cytokine secretion by increasing nuclear localization of some NFκB subtypes. Further studies should be done to determine the prominence of this mechanism in clinical environments.