| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2602550 | Toxicology in Vitro | 2012 | 9 Pages |
Dietary retinoid bioavailability involves the interplay of the intestine (transport and metabolism) and the liver (secondary metabolism). To reproduce these processes in vitro, differentiated human intestinal Caco-2/TC7 cells were co-cultured with two hepatocyte cell lines. Murine 3A cells and the more highly differentiated human HepaRG hepatocytes were both shown to respond to β-carotene (BC) and retinol (ROH) treatment by secreting Retinol Binding Protein 4 (RBP4). In co-culture experiments, Caco-2/TC7 were differentiated on filter inserts and transferred for the time of the experiment to culture wells containing confluent 3A or differentiated HepaRG cells. Functionality of the co-cultures was assayed using as endpoints the retinol-dependent secretion of RBP4 and the retinoic acid-dependent induction of CYP26A1 in hepatocytes. BC and ROH added to intestinal Caco-2/TC7 induced a reduction in intracellular RBP4 levels in the underlying hepatocytes and its secretion into the medium. HepaRG hepatocytes were also shown to up-regulate the expression of CYP26A1 mRNA in response to retinoid treatment. This in vitro model represents a useful tool to analyze the absorption and metabolism of retinoids and could be further developed to investigate other dietary compounds and molecules of pharmacological interest.
► An in vitro co-culture system of human differentiated intestinal and hepatic cells is presented. ► The interplay between intestine and liver transport and metabolism was tested using dietary retinoids. ► Beta-carotene and retinol given to enterocytes acted on retinoid metabolism of co-cultured hepatocytes. ► For the homologous “all human” system we used highly differentiated human HepaRG hepatocytes.
