Inhibition by deacetylase inhibitors of IL-1-dependent induction of haptoglobin involves CCAAT/Enhancer-binding protein isoforms in intestinal epithelial cells.

Abstract:

:Intestinal epithelial cells participate in an acute phase response (APR) by responding to cytokines and by expressing acute phase protein genes. We hypothesized that butyrate, a fermentation product of the bacterial intestinal flora with deacetylase activity, affects the APR in intestinal epithelial cells. Sodium butyrate (NaBu) and Trichostatin A (TSA) induced alkaline phosphatase activity and histone H4 acetylation in IEC-6 rat intestinal epithelial cells treated with or without interleukin-1beta (IL-1). In contrast, both NaBu and TSA attenuated the IL-1-dependent induction of the acute phase protein gene haptoglobin, as well as C/EBPbeta and C/EBPdelta transcription factors mRNAs. Gel shift and supershift assays showed a strong decrease in the IL-1-induced C/EBPbeta and C/EBPdelta containing complexes binding to the HaptoA C/EBP DNA-binding site of the haptoglobin promoter, by NaBu and TSA. Furthermore, site-specific mutation of the HaptoA site abolished the NaBu- and TSA-dependent inhibition of haptoglobin, as determined by transient transfection assays. These results suggest that deacetylase inhibitors may regulate the IL-1 dependent induction of haptoglobin by down-regulating C/EBP isoforms, and that C/EBPs represent a target for the action of butyrate in the control of the APR of intestinal epithelial cells.

authors

Désilets A,Gheorghiu I,Yu SJ,Seidman EG,Asselin C

doi

10.1006/bbrc.2000.3531

subject

Has Abstract

pub_date

2000-09-24 00:00:00

pages

673-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(00)93531-9

journal_volume

276

pub_type

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