Sodium arsenite downregulates transcriptional activity of AP-1 and CRE binding proteins in IL-1β-treated Caco-2 cells by increasing the expression of the transcriptional repressor CREMα

Dan D. Hershko, Bruce W. Robb, Guang Jo Luo, Eric S. Hungness, Per Olof Hasselgren

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

In recent studies, sodium arsenite (SA) inhibited IL-6 production in cultured intestinal epithelial cells, at least in part by downregulating the activity of nuclear factor-kappaB (NF-κB). The influence of SA on the activity of other transcription factors regulating the interleukin-6 (IL-6) gene in enterocytes is not known. We tested the effect of SA on the activity of CCAAT/enhancer binding protein (C/EBP), activating protein-1 (AP-1), and CRE binding proteins in IL-1βtreated Caco-2 cells. DNA binding activity was determined by electrophoretic mobility shift assay (EMSA) and transcriptional activity by transfecting cells with luciferase reporter plasmids containing promoter constructs with binding sites for the individual transcription factors. DNA binding activity for all three transcription factors was increased after treatment with SA or IL-1β. In contrast, SA inhibited transcriptional activity of AP-1 and CRE binding proteins but not C/EBP. Additional experiments provided evidence that the inhibition of AP-1 and CRE mediated transcriptional activity was associated with, and probably caused by, increased expression of the transcriptional repressor cyclic AMP response element modulator (CREM)α. The present results are consistent with the concept that SA inhibits IL-6 production in stimulated enterocytes by downregulating the transcriptional activity of several, but not all, IL-6-related transcription factors. Because of the multiple important biological functions of IL-6 in the enterocyte and gut mucosa, methods to regulate enterocyte IL-6 production have significant clinical implications.

Original languageEnglish (US)
Pages (from-to)627-640
Number of pages14
JournalJournal of Cellular Biochemistry
Volume90
Issue number3
DOIs
StatePublished - Oct 15 2003
Externally publishedYes

Keywords

  • Cytokines
  • Enterocytes
  • IL-6
  • Intestine
  • Mucosa
  • Sodium arsenite
  • Transcription factors

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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