Tumour necrosis factor alpha regulates iron transport and transporter expression in human intestinal epithelial cells.
TNFalpha has dramatic effects on iron metabolism contributing to the generation of hypoferraemia in the anaemia of chronic disease. Interestingly, TNFalpha is also synthesised and released within the intestinal mucosa, suggesting that this pro-inflammatory cytokine may play a role in regulating dietary iron absorption. To investigate this possibility, we stimulated intestinal Caco-2 cells with TNFalpha (10 ng/ml). In TNFalpha-treated cells, apical iron uptake was significantly decreased and this was accompanied by a reduction in divalent metal transporter protein and mRNA expression. Our data suggest that TNFalpha could regulate dietary iron absorption and that the apical transport machinery is the target for these actions.
Johnson
Deborah
D
School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.
Bayele
Henry
H
Johnston
Kelly
K
Tennant
Jason
J
Srai
Surjit Kaila
SK
Sharp
Paul
P
D001692:Biological Transport / Q000187:drug effects*; D018938:Caco-2 Cells; D027682:Cation Transport Proteins / Q000235:genetics; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007422:Intestines / Q000166:cytology*; D007501:Iron / Q000378:metabolism*; D033862:Iron-Binding Proteins / Q000235:genetics; D026901:Membrane Transport Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D000098742:Ferroportin
D027682:Cation Transport Proteins; D033862:Iron-Binding Proteins; D026901:Membrane Transport Proteins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; D014409:Tumor Necrosis Factor-alpha; D000098742:Ferroportin; D005293:Ferritins; D007501:Iron