Special section on drug metabolism and the microbiome: Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes

Yating Cheng, Un Ho Jin, Clint D. Allred, Arul Jayaraman, Robert S. Chapkin, Stephen Safe

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The tryptophan microbiota metabolites indole-3-acetate, indole-3-aldehyde, indole, and tryptamine are aryl hydrocarbon receptor (AhR) ligands, and in this study we investigated their AhR agonist and antagonist activities in nontransformed young adult mouse colonocyte (YAMC) cells. Using Cyp1a1 mRNA as an Ah-responsive end point, we observed that the tryptophan metabolites were weak AhR agonists and partial antagonists in YAMC cells, and the pattern of activity was different from that previously observed in CaCo2 colon cancer cells. However, expansion of the end points to other Ah-responsive genes including the Cyp1b1, the AhR repressor (Ahrr), and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP-ribose) poly-merase (TiParp) revealed a highly complex pattern of AhR agonist/antagonist activities that were both ligand- and gene-dependent. For example, the magnitude of induction of Cyp1b1 mRNA was similar for TCDD, tryptamine, and indole-3-acetate, whereas lower induction was observed for indole and indole-3-aldehyde was inactive. These results suggest that the tryptophan metabolites identified in microbiota are selective AhR modulators.

Original languageEnglish (US)
Pages (from-to)1536-1543
Number of pages8
JournalDrug Metabolism and Disposition
Volume43
Issue number10
DOIs
StatePublished - Oct 1 2015

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Fingerprint Dive into the research topics of 'Special section on drug metabolism and the microbiome: Aryl hydrocarbon receptor activity of tryptophan metabolites in young adult mouse colonocytes'. Together they form a unique fingerprint.

Cite this