Butyrate modulates gene and protein expression in human intestinal endothelial cells

Hitoshi Ogawa, Parvaneh Rafiee, Pamela J. Fisher, Nathan A. Johnson, Mary F. Otterson, David G. Binion

    Research output: Contribution to journalArticle

    47 Citations (Scopus)

    Abstract

    We hypothesized that sodium butyrate, a product of enteric bacterial fermentation, modulates gene expression in gut microvascular endothelium which plays a central role in mucosal immunity. We examined sodium butyrate's effect on LPS-induced gene and protein expression in primary cultures of human intestinal microvascular endothelial cells. cDNA array analysis revealed that sodium butyrate augmented ICAM-1 mRNA expression, while it inhibited IL-6 and COX-2 expression in response to LPS stimulation. These results were confirmed at the protein level. Prostaglandin E2 production by LPS was also strongly inhibited by butyrate. The pattern of altered gene expression by butyrate was reproduced by the histone deacetylase inhibitor tricostatin A, suggesting that the regulatory mechanism of butyrate on HIMEC gene expression involves histone deacetylase inhibition. IκBα degradation and NF-κB activation were unaffected by butyrate. In addition to effects on epithelium, sodium butyrate modulates the innate mucosal immune response towards LPS through effects on microvascular endothelial function.

    Original languageEnglish
    Pages (from-to)512-519
    Number of pages8
    JournalBiochemical and Biophysical Research Communications
    Volume309
    Issue number3
    DOIs
    Publication statusPublished - 2003 Sep 26

    Keywords

    • Cyclooxygenase 2
    • Human intestinal microvascular endothelial cells
    • ICAM-1
    • IL-6
    • Lipopolysaccharide
    • Nuclear factor-κB
    • Prostaglandin E2
    • Sodium butyrate

    ASJC Scopus subject areas

    • Biochemistry
    • Biophysics
    • Molecular Biology

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