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Liver iron homeostasis is altered by colonic inflammation and dietary iron

Chua, A., Ho, D.S., Klopcic, B., Olynyk, J., Lawrance, I.C. and Trinder, D. (2012) Liver iron homeostasis is altered by colonic inflammation and dietary iron. In: Australian Gastroenterology Week 2012, 16 - 19 October 2012, Adelaide Convention Centre, S.A.

Abstract

Background Patients with inflammatory bowel diseases (IBD) develop anaemia of inflammation (AI) due to disturbances in iron homeostasis that limits the availability of iron for erythropoiesis. Aims In this study, the effects of colonic inflammation and dietary iron levels on liver iron homeostasis were investigated in a mouse model of colitis. Methods Colonic inflammation was induced by the administration of dextran sodium sulphate (DSS) to mice fed either an iron-supplemented (1%) or control iron (0.01%) diet. Liver and plasma iron concentrations as well as plasma transferrin saturation were measured biochemically. Liver gene expression was determined by real-time PCR and plasma IL-6 levels were measured by ELISA. Results DSS-induced colonic inflammation increased plasma IL-6 levels. Dietary iron supplementation further enhanced colonic inflammation and plasma IL-6 levels (p < 0.0001). Liver iron and plasma transferrin saturation were elevated in dietary iron-supplemented mice. Post-DSS treatment, liver iron levels increased (p < 0.01) and transferrin saturation decreased (p < 0.01) in mice fed the iron-supplemented and control iron diets, consistent with the presence of AI. Liver expression of the iron regulatory genes, hepcidin (Hamp1) and inhibitor of DNA binding 1 (Id1), was upregulated by dietary iron (p < 0.01) but unexpectedly downregulated by DSS treatment (p < 0.05). Smad7 gene expression was decreased in DSStreated mice and Bmp6 expression was increased by dietary iron supplementation (p < 0.001). Dietary iron supplementation decreased the gene expression of the iron importer transferrin receptor 1 (Tfr1), congruent with the iron-dependent regulation of Tfr1 and expression and further diminished by DSS treatment (p < 0.05). Gene expression of the iron importer Zip14 was increased (p < 0.05) whilst that of the iron exporter ferroportin 1A was decreased (p < 0.0001) with DSS treatment, consistent with the retention of iron by the liver. Conclusion The perturbations in iron homeostasis resulting from increased colonic inflammation observed in this study are consistent with AI. The regulatory pathways for the changes seen, however, are unclear. The lack of induction of Hamp1 expression by plasma IL-6 levels suggests that other regulatory signals may impede hepcidin induction by inflammation. A possible candidate is the erythroid signal as increased erythropoietic activity is known to be a strong negative regulator of hepcidin.

Publication Type: Conference Item
URI: http://researchrepository.murdoch.edu.au/id/eprint/19985
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