Ni(II) ions dysregulate cytokine secretion from human monocytes

Jill B. Lewis, Regina L.W. Messer, Leslie Pitts, Stephen D. Hsu, Jason M. Hansen, John C. Wataha

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


Nickel-containing alloys are used in dentistry because of their low cost, but poor corrosion behavior increases their risk of causing adverse biological responses. Intraorally, nickel-containing alloys accumulate bacterial plaque that triggers periodontal inflammation via toxins such as lipopolysaccharide (LPS). Recent evidence suggests that in monocytes, Ni(II) amplifies LPS-induced secretion of several cytokines that mediate periodontal destruction. Thus, we investigated the effects of Ni(II), with or without LPS, on the secretion of a broader array of cytokines from monocytes. We then measured monocytic expression of two proteins, Nrf2 and thioredoxin-1 (Trx1), that influence the regulation of cytokine secretion. Cytokine arrays were used to measure the effects of 0-50 μM Ni(II) on cytokine secretion from human THP1 monocytes, with or without LPS activation. Immunoblots were used to estimate Nrf2 and Trxl levels. Our results indicate that both Ni(II) alone and Ni(II) with LPS have broad-based effects on cytokine secretion. Ni(II) increased Nrf2 levels by threefold, and LPS amplified the effects of Ni(II) by 10-fold. Trx1 levels did not change under any condition tested. Our results suggest that Ni(II)-induced changes in cytokine secretion by monocytes are diverse and may be influenced by Nrf2 but are not likely influenced by changes in whole-cell Trxl levels.

Original languageEnglish (US)
Pages (from-to)358-365
Number of pages8
JournalJournal of Biomedical Materials Research - Part B Applied Biomaterials
Issue number2
StatePublished - Feb 2009


  • Biocompatibility/hard tissue
  • Biocompatibility/soft tissue
  • Cytokines
  • Inflammation
  • Metal ions

ASJC Scopus subject areas

  • Biomaterials
  • Biomedical Engineering


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