Transferrin-iron and proinflammatory cytokines influence iron status and apical iron transport efficiency of Caco-2 intestinal cell line

Abstract

Endogenous factors that regulate the absorption of dietary iron remain unknown. Differentiated cultures of Caco-2 human intestinal cells grown on membrane inserts were used to study the characteristics of transferrin-iron uptake across the basolateral surface, the effects of transferrin-iron uptake on cellular ferritin content, the transport of apical iron across the monolayer, and the influence of proinflammatory cytokines on these processes. Caco-2 cells accumulated transferrin-iron from the basolateral chamber by a temperature-dependent, saturable process that was enhanced in less differentiated cultures and attenuated by pre-exposure to high-iron medium. Exposure of Caco-2 cells to 10 μmol/L diferric transferrin for 36 hr increased cellular ferritin protein 3.4-fold and decreased the transport of apical 59Fe to the basolateral compartment by 45%. Pretreatment of cells with a combination of interleukin-1β, interleukin-6, and tumor necrosis factor-α increased transferrin-iron uptake by 70% and cellular ferritin content by 54%. Also, cytokine treatment decreased apical iron transport across the monolayer by 40% without altering paracellular transport of mannitol. These results suggest that transferrin-iron and proinflammatory cytokines are capable of modulating the iron status and iron transport activity of intestinal epithelial cells.