Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-kappaB activity.
Previous studies have suggested that the production of interleukin-6 (IL-6) is increased in the intestinal mucosa during inflammation, and that nuclear factor-kappaB (NF-kappaB) 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-kappaB activity. Cultured Caco-2 cells were treated with sodium arsenite and were then stimulated with IL-1beta. IL-6 production and gene expression were determined by ELISA and reverse transcriptase-PCR respectively. NF-kappaB DNA binding activity was determined by electrophoretic mobility shift assay. IL-1beta increased NF-kappaB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-1beta 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-kappaB, the inhibitory effect of sodium arsenite on NF-kappaB 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-kappaB activity.
Hershko
Dan D
DD
Shriners Hospitals for Children, Cincinnati, OH, USA.
Robb
Bruce W
BW
Hungness
Eric S
ES
Luo
Guangju
G
Guo
Xialing
X
Hasselgren
Per-Olof
PO
D018053:Arsenites / Q000494:pharmacology*; D018938:Caco-2 Cells; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D020895:Enterocytes / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017670:Sodium Compounds / Q000494:pharmacology*
D018053:Arsenites; D007375:Interleukin-1; D015850:Interleukin-6; D016328:NF-kappa B; D012333:RNA, Messenger; D011994:Recombinant Proteins; D017670:Sodium Compounds; C017947:sodium arsenite