Ni-induced Changes in Signaling Pathways That Regulate Oxidative Stress and Inflammatory Responses

Abstract

Anecdotal clinical evidence suggests that periodontal inflammation is intensified in tissues adjacent to dental restorations containing nickel alloys. One possible mechanism for this inflammation is the synergism of Ni(II) from corroded restoratives with lipopolysaccharides (LPS) from plaque to increase net secretion of inflammatory cytokines from monocytes. We have found that Ni(II) and LPS interact within peripheral blood monocytes (PBMs) to increase levels of certain proteins involved in oxidative stress and inflammatory signaling pathways. One such protein is nuclear reducing factor 2 (Nr£2) which acts as a transcription factor to increase the production of other proteins involved in the cell's response to oxidative stress. Increased levels of Nrf2 were found within the whole cell and within the nucleus. This finding is consistent with an hypothesis that Ni(II) ions and LPS act together to amplify levels of Nrf2, and Nrf2 target gene products enhance transcription of inflammatory genes and secretion of specific inflammatory cytokines.