Ni(II) activates the Nrf2 signaling pathway in human monocytic cells

Jill B. Lewis, Regina L W Messer, Veronica V. McCloud, Petra E. Lockwood, Stephen Hsu, John C. Wataha

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

Nickel is a component of biomedical alloys that is released during corrosion and causes inflammation in tissues by as yet unknown mechanisms. Recent data show that Ni(II) at concentrations of 10-50 μm amplifies lipopolysaccharide-triggered, NFκB-mediated cytokine secretion from monocytes. In the current study, we tested the hypothesis that Ni(II) amplifies cytokine secretion by activating the Nrf2 antioxidant pathway rather than by enhancing activity of the NFκB signaling pathway. Human THP1 monocytes were exposed to Ni(II) concentrations of 10-30 μm for 6-72 h, then immunoblots of whole-cell lysates or cytosolic and nuclear proteins were used to detect changes in Nrf2 or NFκB signaling. Our results show that Ni(II) increased (by 1-2 fold) whole-cell Nrf2 levels and nuclear translocation of Nrf2, and amplified lipopolysaccharide (LPS)-induction of Nrf2 (by 3-5 fold), but had no detectable effect on the initial activation or nuclear translocation of NFκB. Because Nrf2 target gene products are known regulators of NFκB nuclear activity, our results suggest that Ni(II) may affect cytokine secretion indirectly via modulation of the Nrf2 pathway.

Original languageEnglish (US)
Pages (from-to)5348-5356
Number of pages9
JournalBiomaterials
Volume27
Issue number31
DOIs
StatePublished - Nov 1 2006

Fingerprint

Cytokines
Lipopolysaccharides
Monocytes
Corrosion
Nuclear Proteins
Antioxidants
Nickel
Genes
Chemical activation
Modulation
Tissue
Inflammation

Keywords

  • Biocompatibility
  • Dental alloy
  • Inflammation
  • Monocyte
  • Nickel

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering

Cite this

Ni(II) activates the Nrf2 signaling pathway in human monocytic cells. / Lewis, Jill B.; Messer, Regina L W; McCloud, Veronica V.; Lockwood, Petra E.; Hsu, Stephen; Wataha, John C.

In: Biomaterials, Vol. 27, No. 31, 01.11.2006, p. 5348-5356.

Research output: Contribution to journalArticle

Lewis, Jill B. ; Messer, Regina L W ; McCloud, Veronica V. ; Lockwood, Petra E. ; Hsu, Stephen ; Wataha, John C. / Ni(II) activates the Nrf2 signaling pathway in human monocytic cells. In: Biomaterials. 2006 ; Vol. 27, No. 31. pp. 5348-5356.
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