Ni(II) ions dysregulate cytokine secretion from human monocytes

Area of Science:

• Biomaterials Science
• Immunology
• Oral Biology

Background:

• Nickel-containing alloys are cost-effective dental materials but exhibit poor corrosion resistance.
• Intraoral corrosion of these alloys can lead to bacterial plaque accumulation and periodontal inflammation, mediated by toxins like lipopolysaccharide (LPS).
• Ni(II) ions may exacerbate LPS-induced inflammatory responses in monocytes, crucial cells in periodontal health.

Purpose of the Study:

• To investigate the impact of Ni(II), alone and in combination with LPS, on the secretion of a wide range of cytokines from human monocytes.
• To assess the influence of Ni(II) on the expression of Nrf2 and thioredoxin-1 (Trx1) proteins within monocytes, which are known regulators of cytokine secretion.

Main Methods:

• Human THP1 monocytes were treated with varying concentrations of Ni(II) (0-50 microM), with or without LPS activation.
• Cytokine secretion profiles were analyzed using cytokine arrays.
• Monocytic expression levels of Nrf2 and Trx1 proteins were quantified using immunoblots.

Main Results:

• Both Ni(II) exposure alone and combined Ni(II) with LPS significantly altered the secretion of multiple cytokines.
• Ni(II) treatment led to a threefold increase in Nrf2 protein levels.
• LPS significantly amplified the effect of Ni(II) on Nrf2, resulting in a tenfold increase compared to Ni(II) alone.
• Thioredoxin-1 (Trx1) protein levels remained unchanged across all experimental conditions.

Conclusions:

• Ni(II) induces diverse changes in monocyte cytokine secretion, suggesting a complex role in inflammatory processes.
• The observed alterations in cytokine secretion may be influenced by Ni(II)-mediated upregulation of Nrf2.
• Changes in whole-cell Trx1 levels do not appear to be a significant factor in Ni(II)-modulated cytokine responses in monocytes.