The glucocorticoid mometasone furoate is a novel FXR ligand that decreases inflammatory but not metabolic gene expression.

ABSTRACT: The Farnesoid X receptor (FXR) regulates bile salt, glucose and cholesterol homeostasis by binding to DNA response elements, thereby activating gene expression (direct transactivation). FXR also inhibits the immune response via tethering to NF-κB (tethering transrepression). FXR activation therefore has therapeutic potential for liver and intestinal inflammatory diseases. We aim to identify and develop gene-selective FXR modulators, which repress inflammation, but do not interfere with its metabolic capacity. In a high-throughput reporter-based screen, mometasone furoate (MF) was identified as a compound that reduced NF-κB reporter activity in an FXR-dependent manner. MF reduced mRNA expression of pro-inflammatory cytokines, and induction of direct FXR target genes in HepG2-GFP-FXR cells a

SUBMITTER: Bijsmans IT 

PROVIDER: S-EPMC4572934 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature