Effect of subtoxic concentrations of metal ions on NFκB activation in THP‐1 human monocytes

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Abstract
THP-1 human monocytes and human peripheral blood monocytes have altered inflammatory cytokine secretion profiles after exposure to a variety of metal ions known to be released from biomaterials. Transcriptional regulation of these cytokines often involves activation of the transcription factor NFκB. The present study was designed to determine whether metal ion treatment of monocytes results in changes in levels of activated NFκB. THP-1 cells were grown in suspension in the presence of sublethal concentrations of ions of Ag+, Co2+, Cu2+, Hg2+, Ni2+, and Pd2+. After 24 h of exposure to metal ions, the cells were harvested, counted, and the nuclear proteins extracted. Electrophoretic mobility shift assays were performed using a 32P-ATP end-labeled oligonucleotide consensus sequence for the NFκB transcription factor. DNA/protein complexes were quantified by phosphorimage analysis and compared by ANOVA (Tukey, α = 0.05). Exposure of THP-1 cells to 100 μM of Pd2+ caused a significant increase in activated NFκB (p < 0.05) whereas treatment with 5 μM of Ag+ resulted in significantly decreased levels of nuclear NFκB (p < 0.05). No other metal ions tested caused a significant change in basal levels of nuclear NFκB (Co2+, Hg2+, Ni2+, and Cu2+). However, exposure to 50 μM of Cu2+ resulted in a reproducible, though not significant, increase in nuclear NFκB levels. These results indicate that inflammatory responses to some metal ions may be influenced by NFκB-mediated transcriptional regulation. © 2002 Wiley Periodicals, Inc. J Biomed Mater Res 64A: 217–224, 2003