Effects of rifampicin on global gene expression in human small intestine.
OBJECTIVE
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.


CONCLUSIONS
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.
Oscarson
Mikael
M
Division of Pharmacology/Neurobiology, Biozentrum, University of Basel, Basel, Switzerland.
Burk
Oliver
O
Winter
Stefan
S
Schwab
Matthias
M
Wolbold
Renzo
R
Dippon
Juergen
J
Eichelbaum
Michel
M
Meyer
Urs A
UA
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D015415:Biomarkers / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012293:Rifampin / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D000904:Antibiotics, Antitubercular; D015415:Biomarkers; D012333:RNA, Messenger; D012293:Rifampin