Metal ions potentiate microglia responsiveness to endotoxin

Area of Science:

• Neuroimmunology
• Toxicology
• Oral Medicine

Background:

• Oral metal exposure is linked to neurotoxicity.
• Dental metals activate immune cells like dendritic cells (MoDCs).
• The impact of low-level dental metals on brain-resident immune cells remains unclear.

Purpose of the Study:

• To investigate if dental metals activate primary human microglia and THP-1 cells in vitro.
• To assess the effect of near-physiological metal concentrations on microglia and THP-1 cell responsiveness to lipopolysaccharide (LPS).

Main Methods:

• Exposure of primary human microglia and monocytic THP-1 cells to various dental metals (Cr, Fe, Co, Ni, Cu, Zn, Au, Hg) at high non-toxic and near-physiological concentrations.
• Measurement of Interleukin-8 (IL-8) and Interleukin-6 (IL-6) production as indicators of immune activation.
• Evaluation of changes in LPS responsiveness following metal exposure.

Main Results:

• High concentrations of most transition metals (except Cr) induced IL-8 and IL-6 in microglia, with Ni and Co being most potent.
• At near-physiological doses, zinc (Zn) and copper (Cu) significantly induced IL-8 production.
• Zn and Cu markedly potentiated LPS-induced responses in both microglia and THP-1 cells.

Conclusions:

• Transition metals can activate microglia, similar to MoDCs.
• Zn and Cu are key mediators of innate immune activation at near-physiological concentrations.
• Synergistic effects between Zn/Cu and LPS suggest a potential link to oral metal-induced neurotoxicity.