Intracellular iron regulates iron absorption and IRP activity in intestinal epithelial (Caco-2) cells

In vertebrates, body Fe homeostasis is maintained through the regulation of its intestinal absorption. In addition, because Fe is both essential and toxic, intracellular Fe levels are tightly regulated. Consequently, intestinal epithelial cells are in the unique position of being responsible simultaneously for the regulation of body Fe absorption and the regulation of their intracellular Fe levels to remain viable. We tested the hypothesis that the regulation of transepithelial Fe transport and the regulation of intracellular Fe levels are sensitive to a common effector. To this end, we used a recently developed protocol to obtain cultured intestinal epithelial cells with defined intracellular Fe concentrations. In these cells we tested Fe absorption and Fe regulatory protein (IRP) activities. We found that transepithelial Fe transport was inversely related to 20-200 μM intracellular Fe and that Caco-2 cells expressed Fe regulatory protein-1 and Fe regulatory protein-2 activities. Fe regulatory protein-1 activity, Fe regulatory protein-2 mass, transferrin receptor density, and ferritin levels were regulated by intracellular Fe in the same range (20-200 μM) that affected transepithelial Fe transport. These results suggest that a common Fe-responsive factor regulates both intracellular Fe levels and Fe absorption by Caco-2 cells.