Dietary AhR Ligands Have No Anti-Fibrotic Properties in TGF-β1-Stimulated Human Colonic Fibroblasts

Abstract

Background: Intestinal fibrosis is a common complication in inflammatory bowel disease (IBD) patients without specific treatment. Aryl hydrocarbon receptor (AhR) activation is associated with better outcomes in intestinal inflammation. Development of novel therapies targeting fibrogenic pathways is required and we aimed to screen dietary AhR ligands for their anti-fibrotic properties in TGF-β1-stimulated human colonic fibroblast cells. Methods: The study was conducted using TGF-β1-stimulated CCD-18Co, a human colonic fibroblast cell line in response to increased concentrations of dietary ligands of AhR such as FICZ, ITE, L-kynurenine and curcumin. Fibrosis markers such as α-SMA, COL1A1, COL3A1 and CTGF were assessed. AhR and ANRT RNA were evaluated. Results: TGF-β1 at 10 ng/mL significantly induced mRNA levels for ECM-associated proteins such as CTGF, COL1A1 and COL3A1 in CCD-18Co cells. FICZ from 10 to 1000 nM, L-kynurenine from 0.1 to 10 μM, ITE from 1 to 100 μM or curcumin from 5 to 20 μM had no significant effect on fibrosis markers in TGF-β1-induced CCD-18Co. Conclusions: Our data highlight that none of the tested dietary AhR ligands had an effect on fibrosis markers in TGF-β1-stimulated human colonic fibroblast cells in our experimental conditions. Further studies are now required to identify novel potential targets in intestinal fibrosis.