Previous studies have suggested that the production of interleukin-6 (IL-6) is increased in the intestinal mucosa during inflammation, and that nuclear factor-κB (NF-κB) is an important regulator of the IL-6 gene in the enterocyte. We tested the hypothesis that sodium arsenite inhibits IL-6 production in stimulated enterocytes and that this effect of arsenite is caused by down-regulation of NF-κB activity. Cultured Caco-2 cells were treated with sodium arsenite and were then stimulated with IL-1β. IL-6 production and gene expression were determined by ELISA and reverse transcriptase–PCR respectively. NF-κB DNA binding activity was determined by electrophoretic mobility shift assay. IL-1β increased NF-κB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-1β were inhibited by treatment of the cells with sodium arsenite in a dose- and time-dependent fashion. When cells were transfected with a plasmid expressing the p65 subunit of NF-κB, the inhibitory effect of sodium arsenite on NF-κB activity and IL-6 production was blunted. These results suggest that sodium arsenite inhibits IL-6 production in enterocytes subjected to an inflammatory stimulus, and that this effect, at least in part, reflects down-regulated NF-κB activity.
Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity
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Dan D. HERSHKO, Bruce W. ROBB, Eric S. HUNGNESS, Guangju LUO, Xialing GUO, Per-Olof HASSELGREN; Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity. Clin Sci (Lond) 1 October 2002; 103 (4): 381–390. doi: https://doi.org/10.1042/cs1030381
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