Effects of rifampicin on global gene expression in human small intestine

Pharmacogenet Genomics. 2007 Nov;17(11):907-18. doi: 10.1097/FPC.0b013e3280143dfc.

Abstract

Objectives: The small intestinal wall serves as an important barrier for the entry of foreign substances into the organism. Of particular importance are enzymes and transporters that can inactivate or prevent the uptake of many xenobiotics including drugs. Some of the genes encoding these proteins are transcriptionally activated by xenobiotics, a response well studied in liver but less so in the intestine. The effect of the inducer drug rifampicin on intestinal cells was therefore evaluated both in vivo and in vitro.

Methods: Seven healthy volunteers were treated with rifampicin for 9 days and the global gene expression profile was analysed in RNA from duodenal biopsies taken before and after drug treatment. The gene expression profile was also assessed in LS174T cells derived from a human colon adenocarcinoma after exposure to 10 micromol/l rifampicin for 24 h.

Results: We identified 32 genes that were upregulated and two genes that were downregulated by rifampicin treatment in vivo. The list of rifampicin regulated transcripts expectedly included drug metabolizing enzymes and drug transporters, but also genes involved in lipid and amino acid metabolism as well as genes not previously recognized to be part of the adaptation of intestinal cells to xenobiotic exposure. Only a limited number of these rifampicin-regulated transcripts were however also regulated by rifampicin in LS174T cells.

Conclusion: The similarities and differences of changes in gene expression after rifampicin treatment between duodenal biopsies and cell culture provide a new assessment of the extent and diversity of systems affected by drug exposure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Antibiotics, Antitubercular / pharmacology*
  • Biomarkers / metabolism
  • Colonic Neoplasms / drug therapy
  • Colonic Neoplasms / metabolism
  • Colonic Neoplasms / pathology
  • Duodenum / drug effects*
  • Duodenum / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation / drug effects*
  • Humans
  • Oligonucleotide Array Sequence Analysis
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rifampin / pharmacology*
  • Transcription, Genetic / drug effects
  • Transcription, Genetic / genetics
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / pathology

Substances

  • Antibiotics, Antitubercular
  • Biomarkers
  • RNA, Messenger
  • Rifampin