Proceedings of The Physiological Society

Europhysiology 2018 (London, UK) (2018) Proc Physiol Soc 41, PCB109

Poster Communications

Bile Acids Regulate Expression of Aryl Hydrocarbon Receptor in Colonic Epithelial Cells.

C. G. Clerkin1, J. Smyth1, C. M. Fallon1, N. K. Lajczak-McGinley1, S. J. Keely1

1. Molecular Medicine, Royal College of Surgeons, Dublin, Ireland.

The aryl hyrdrocarbon receptor (AHR) is expressed in the colonic mucosa, where it acts as a receptor for numerous substances, including bilirubin. Activation of AHR by endogenous ligands has been reported to suppress mucosal immune cell activation and to prevent inflammation. However, factors that regulate the expression of AHR in the colonic epithelium are still poorly understood. Here, we set out to conduct a preliminary investigation of the potential role for bile acids in regulation of colonic epithelial AHR expression. T84 colonic epithelial cells were grown as polarised monolayers on transparent permeable supports until they reached a transepithelial electrical resistance of 1000 Ωcm-2. Cells were treated for various periods of time (0 - 48 hrs) with the most common human colonic bile acid, deoxycholic acid (DCA, 150 µM), or with GW4064 (5 µM), a specific agonist of the nuclear bile acid receptor, FXR. Levels of the gene transcript, AHR were quantified by RT-qPCR and the data were expressed as the mean ± SEM fold change (2-ΔΔCT) in expression. Treatment of T84 cells with DCA, resulted in an increase over time (0-48 hrs) in the expression of AHR. Maximal responses to DCA occurred after 48 hrs at which time expression of AHR mRNA was 5.48 ± 0.05 fold of that in control cells (n=4). To determine if the actions of DCA might be mediated by activation of FXR, cells were treated with the selective agonist, GW4064. However, in contrast to DCA, GW4064 downregulated AHR expression by 0.53 ± 0.01 fold after 48 hrs of treatment (n=3). These data suggest that luminal bile acids have the capacity to modulate AHR expression in the colonic epithelium. Such actions may be important in the setting of colonic inflammation and future studies will aim to elucidate the physiological significance and molecular mechanisms involved.

Where applicable, experiments conform with Society ethical requirements