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.

Identifying immune cell infiltration and effective diagnostic biomarkers in Crohn’s disease by bioinformatics analysis

“…CXCL10, an inflammatory chemokine that could be induced by IFN-γ, was produced by neutrophils, fibroblasts, and dendritic cells, homing leukocytes to inflamed tissues and causing the persistence of inflammation ( 35 , 36 ), and played a role in the pathogenesis of several autoimmune system diseases ( 37 ). COL1A1 was significantly elevated in the intestinal fibrosis phenotype ( 38 , 39 ).…”

Impact of Different Nutrition Strategies on Patients with Inflammatory Bowel Disease (IBD)

“…Amamou et al [ 10 ] studied possible novel dietary therapies against intestinal fibrosis via aryl hydrocarbon receptor (AhR) ligands. The authors, through their in vitro study, tried to depict the effects of different dietary AhR ligands on intestinal fibrosis and, more specifically, the stimulation of TGF-1, which seems to trigger fibrotic mechanism in intestinal tissue.…”

“…This lacking effect, according to the authors, may be due to incubation time, cell type, the fibroblastic process step, or the kind of AhR ligands chosen. Therefore, it is noted that further studies are required to examine the potential novelty of that method in intestinal fibrosis [ 10 ].…”