Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity

Dan D. Hershko, Bruce Robb, Eric S. Hungness, Guangju Luo, Xialing Guo, Per Olof Hasselgren

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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-Iβ. 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-Iβ increased NF-κB DNA binding activity, IL-6 mRNA levels and IL-6 production. These effects of IL-Iβ 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.

Original languageEnglish (US)
Pages (from-to)381-390
Number of pages10
JournalClinical Science
Volume103
Issue number4
StatePublished - Oct 1 2002
Externally publishedYes

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Interleukin-6
Epithelial Cells
Enterocytes
NFI Transcription Factors
Caco-2 Cells
arsenite
DNA
Electrophoretic Mobility Shift Assay
Intestinal Mucosa
Reverse Transcriptase Polymerase Chain Reaction
Cultured Cells
Plasmids
Down-Regulation
Enzyme-Linked Immunosorbent Assay
sodium arsenite
Inflammation
Gene Expression
Messenger RNA
Genes

Keywords

  • Cytokines
  • Inflammation
  • Intestine
  • Mucosa

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity. / Hershko, Dan D.; Robb, Bruce; Hungness, Eric S.; Luo, Guangju; Guo, Xialing; Hasselgren, Per Olof.

In: Clinical Science, Vol. 103, No. 4, 01.10.2002, p. 381-390.

Research output: Contribution to journalArticle

Hershko, Dan D. ; Robb, Bruce ; Hungness, Eric S. ; Luo, Guangju ; Guo, Xialing ; Hasselgren, Per Olof. / Arsenite inhibits interleukin-6 production in human intestinal epithelial cells by down-regulating nuclear factor-κB activity. In: Clinical Science. 2002 ; Vol. 103, No. 4. pp. 381-390.
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