Endogenous Tryptophan-Derived Ah Receptor Ligands are Dissociated from CYP1A1/1B1-Dependent Negative-Feedback.

ABSTRACT: The aryl hydrocarbon receptor (AHR) exerts major roles in xenobiotic metabolism, and in immune and barrier tissue homeostasis. How AHR activity is regulated by the availability of endogenous ligands is poorly understood. Potent AHR ligands have been shown to exhibit a negative feedback loop through induction of CYP1A1, leading to metabolism of the ligand. Our recent study identified and quantified 6 tryptophan metabolites (eg, indole-3-propionic acid, and indole-3-acetic acid) in mouse and human serum, generated by the host and gut microbiome, that are present in sufficient concentrations to individually activate the AHR. Here, these metabolites are not significantly metabolized by CYP1A1/1B1 in an in vitro metabolism assay. In contrast, CYP1A1/1B metabolizes the potent endogenous AHR liga

SUBMITTER: Dong F 

PROVIDER: S-EPMC10331327 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature