Zinc, cadmium and nickel increase the activation of NF-κB and the release of cytokines from THP-1 monocytic cells

Abstract

The sustained activation of the transcription factor nuclear factor κB (NF-κB) by metal-activated signalling pathways can lead to chronic inflammatory processes and related diseases, including carcinogenesis. The aim of the present work was to clarify the effect of zinc, nickel and cadmium on NF-κB activation in the THP-1 human monocytic leukemia cell line. The production of the NF-κB downstream pro-inflammatory mediators tumor necrosis factor (TNF)-α and interleukin (IL)-1β, IL-6 and IL-8 was also evaluated due to their important roles in the pathogenesis of chronic inflammatory and autoimmune diseases and, ultimately, in the development of cancer. The results obtained demonstrated that zinc, nickel and cadmium significantly activate NF-κB, and the release of the chemokine IL-8. Cadmium also induced the release of TNF-α and IL-6 in THP-1 monocytic cells, which may indicate some potential to induce deleterious effects through this pathway.