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Cadmium induces interleukin-8 production via NF-kappaB activation in the human intestinal epithelial cell, Caco-2.

Abstract：

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

journal_name

Cytokine

journal_title

Cytokine

authors

Hyun JS,Satsu H,Shimizu M

doi

10.1016/j.cyto.2007.02.011

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

26-34

issue

1

eissn

1043-4666

issn

1096-0023

pii

S1043-4666(07)00026-9

journal_volume

37

pub_type

杂志文章

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