Tumour necrosis factor alpha regulates iron transport and transporter expression in human intestinal epithelial cells

Abstract

TNFa has dramatic effects on iron metabolism contributing to the generation of hypoferraemia in the anaemia of chronic disease. Interestingly, TNFa is also synthesised and released within the intestinal mucosa, suggesting that this proinflammatory cytokine may play a role in regulating dietary iron absorption. To investigate this possibility, we stimulated intestinal Caco-2 cells with TNFa (10 ng/ml). In TNFa-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 TNFa could regulate dietary iron absorption and that the apical transport machinery is the target for these actions.

Pathogenesis and treatment of anemia in inflammatory bowel disease

“…The presence of ACD should not, therefore, prevent the administration of iron in this population of patients. Oral iron is, however, poorly absorbed because of the inhibition of iron absorption in the duodenum as a result of the combined actions of hepcidin and TNF-α, 4,5,15 which was nicely demonstrated in a clinical study of patients suffering from anemia and IBD. 23 For this reason, the intravenous route of iron administration is preferable and recommended, 14 particularly in patients with ACD/IDA receiving erythropoeisis-stimulating agents (ESA).…”

“…Hepdicin exerts its biological function upon binding to the only known cellular iron exporter, ferroportin (SLC40A1), thereby leading to ferroportin internalization and degradation. 4 This blocks the transfer of absorbed iron from the duodenal enterocyte into the circulation -an effect which can be aggravated by tumor necrosis factor (TNF)-α 5 -and, in parallel, causes retention of iron within macrophages and monocytes. 6 The latter effect is of major importance, because macrophages are involved in the re-utilization of iron from senescent red blood cells which are taken up via erythrophagocytosis.…”

Anemia of chronic disease and defective erythropoietin production in patients with celiac disease

“…35 Thus, iron malabsorption in celiac disease seems to be linked to loss of microvilli in the proximal duodenum, the main site of iron absorption, rather than to inhibition of iron transport at the cellular level. However, since tumor necrosis factor-α reduces iron transport in intestinal cell lines, 36,37 it is possible that a reduction in iron uptake capability by the enterocyte occurs in celiac disease patients with ACD. According to the follow-up data, the response of anemic patients to a gluten-free diet was not influenced by the presence of ACD; this suggests that gluten-induced inflammatory responses in the intestinal mucosa have a primary role in determining the malabsorption of iron/vitamins and the dysregulation of iron homeostasis and ineffective erythropoietin production that, in some patients, lead to ACD.…”

Circulating Soluble Transferrin Receptor According to Glucose Tolerance Status and Insulin Sensitivity

“…In this sense, we were intrigued for the positive association between C-reactive protein and serum sTfR concentration. Different cytokines upregulate TfR expression in in vitro models (15,16). It is possible that different inflammatory factors lead to a spurious increase in serum sTfR in subjects with altered glucose tolerance and that treatment with aspirin or statins correct to some extent this increase.…”