Inflammation-Induced Downregulation of Butyrate Uptake and Oxidation Is Not Caused by a Reduced Gene Expression

J Cell Physiol. 2015 Feb;230(2):418-26. doi: 10.1002/jcp.24725.

Abstract

In ulcerative colitis (UC) the butyrate metabolism is impaired, leading to energy-deficiency in the colonic cells. The effect of inflammation on the butyrate metabolism was investigated. HT-29 cells were incubated with pro-inflammatory cytokines (TNF-α and/or IFN-γ) for 1 and 24 h. Cells were additionally stimulated with butyrate to investigate its anti-inflammatory potential. Butyrate uptake and oxidation were measured using (14)C-labeled butyrate. Gene expression of the butyrate metabolism enzymes, interleukin 8 (IL-8; inflammatory marker) and villin-1 (VIL-1; epithelial cell damage marker) was measured via quantitative RT-PCR. Significantly increased IL-8 expression and decreased VIL-1 expression after 24 h incubation with TNF-α and/or IFN-γ confirmed the presence of inflammation. These conditions induced a decrease of both butyrate uptake and oxidation, whereas the gene expression was not reduced. Simultaneous incubation with butyrate counteracted the reduced butyrate oxidation. In contrast, 1 h incubation with TNF-α induced a significant increased IL-8 expression and decreased butyrate uptake. Incubation with TNF-α and/or IFN-γ for 1 h did not induce cell damage nor influence butyrate oxidation. The inflammation-induced downregulation of the butyrate metabolism was not caused by a reduced gene expression, but appeared consequential to a decreased butyrate uptake. Increasing the luminal butyrate levels might have therapeutic potential in UC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology
  • Butyrates / metabolism
  • Butyrates / pharmacology*
  • Cytokines / metabolism
  • Down-Regulation / drug effects
  • Epithelial Cells / drug effects
  • Epithelial Cells / metabolism
  • Gene Expression / drug effects*
  • HT29 Cells
  • Humans
  • Inflammation / metabolism*
  • Oxidation-Reduction / drug effects*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Butyrates
  • Cytokines
  • Tumor Necrosis Factor-alpha