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

• Published in: Cytokine (Philadelphia, Pa.) Vol. 37; no. 1; pp. 26 - 34
• Main Authors: Hyun, Ja Shil, Satsu, Hideo, Shimizu, Makoto
• Format: Journal Article
• Language: English
• Published: 01.01.2007
• ISSN: 1043-4666
• DOI: 10.1016/j.cyto.2007.02.011

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- alpha and IFN- gamma 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- mu B inhibitor, suppressed the IL-8 secretion in Caco-2 cells. Site-directed mutation of the NF- mu B 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- mu B knock-down Caco-2 cell line that had been stably established by the RNAi method. The increase in translocation of the NF- mu B protein into the nucleus and I- mu B alpha 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- mu B via I- mu B alpha degradation.