TRANSFERRIN-IRON AND PROINFLAMMATORY CYTOKINES INFLUENCE IRON STATUS AND APICAL IRON TRANSPORT EFFICIENCY OF CACO-2 INTESTINAL-CELL LINE

Endogenous factors that regulate the absorption of dietary iron remain unknown. Differentiated cultures of Caco-2 human intestinal cells gro wn on membrane inserts were used to study the characteristics of trans ferrin-iron uptake across the basolateral surface, the effects of tran sferrin-iron uptake on cellular ferritin content, the transport of api cal iron across the monolayer, and the influence of proinflammatory cy tokines on these processes. Caco-2 cells accumulated transferrin-iron from the basolateral chamber by a temperature-dependent, saturable pro cess that was enhanced in less differential cultures and attenuated by pre-exposure to high-iron medium. Exposure of Caco-2 cells to 10 mu m ol/L diferric transferrin for 36 hr increased cellular ferritin protei n 3.4-fold and decreased the transport of apical Fe-59 to the basolate ral compartment by 45%. Pretreatment of cells with a combination of in terleukin-1 beta, interleukin-6, and tumor necrosis factor-alpha incre ased transferrin-iron uptake by 70% and cellular ferritin content by 5 4%. Also, cytokine treatment decreased apical iron transport across th e monolayer by 40% without altering paracellular transport of mannitol . These results suggest that transferrin-iron and proinflammatory cyto kines are capable of modulating the iron status and iron transport act ivity of intestinal epithelial cells. (C) Elsevier Science Inc. 1997.