The IDO inhibitor 1-methyl tryptophan activates the aryl hydrocarbon receptor response in mesenchymal stromal cells.

ABSTRACT: The catabolism of tryptophan (Trp) by indoleamine 2,3-dioxygenase (IDO) is a key step in tolerance effected by a variety of cell types, including mesenchymal stromal cells (MSCs). Trp catabolism generates molecules known as kynurenines, whose tolerance mechanisms involve activation of the Aryl Hydrocarbon Receptor (AHR). A synthetic analog of Trp, 1-methyl tryptophan (1MT), is a selective inhibitor of IDO enzymatic activity being utilized in cancer immunotherapy trials. We hypothesized 1MT might activate AHR independently of its effects on IDO. We demonstrate MSCs express AHR protein, and that in vitro treatment with 1MT causes AHR nucleotranslocation. Upon analyzing mRNA, we observed transcriptional upregulation of cytochrome p450 1a1 and 1b1 by 1MT racemic mixture (R-MT), consiste

SUBMITTER: Lewis HC 

PROVIDER: S-EPMC5696151 | biostudies-literature | 2017 Nov

REPOSITORIES: biostudies-literature