Cadmium induces Interleukin-8 production via NF-κB activation in the human intestinal epithelial cell, Caco-2

In the present study, we investigated the effect of CdCl2 on the inflammatory cytokines in human intestinal Caco-2 cells. The secretion of IL-8 from Caco-2 cells was significantly increased in a dose- and time-dependent manner, whereas the secretion of such other inflammatory cytokines as TNF-α and IFN-γ was not changed. And IL-8 mRNA level was significantly increased by exposing the cells to CdCl2. A reporter vector containing the IL-8 promoter region was then constructed to determine the IL-8 transcriptional activity. The results of this assay demonstrated that the transcriptional activity of IL-8 was increased by CdCl2. Treatment with PDTC, an NF-κB inhibitor, suppressed the IL-8 secretion in Caco-2 cells. Site-directed mutation of the NF-κB consensus element in the human IL-8 promoter abolished the increased transcriptional activity by CdCl2. The increased transcriptional activity caused by CdCl2 was also suppressed in an NF-κB knock-down Caco-2 cell line that had been stably established by the RNAi method. The increase in translocation of the NF-κB protein into the nucleus and I-κBα degradation resulting from CdCl2 stimulation was also confirmed by a Western analysis. Our results suggest that CdCl2 induced IL-8 secretion, its transcription, and its transcriptional activation regulated by NF-κB via I-κBα degradation.